Brooke was born in Portsmouth, New Hampshire, the only child of John Henry Russell, Jr. (1872–1947), the 16th Commandant of the Marine Corps, and his wife, Mabel Cecile Hornby Howard (1879–1967). Her paternal grandfather John Henry Russell, Sr. was a rear admiral in the U.S. Navy. She was named for her maternal grandmother (Roberta) and was known as Bobby to close friends and family.  Due to her father’s career, she spent much of her childhood living in China, the Dominican Republic, Haiti, and other places. Also, she briefly attended The Madeira School in 1919 but graduated from the Holton-Arms School in Bethesda, Maryland.

She married her first husband, John Dryden Kuser (1897–1964), shortly after her seventeenth birthday, on April 26, 1919, in Washington, D.C. “I certainly wouldn’t advise getting married that young to anyone,” she said later in life. “At the age of sixteen, you’re not jelled yet. The first thing you look at, you fall in love with.”  John was the son of the financier and conservationist Anthony Rudolph Kuser and Susie Fairfield Drydan. Susie’s father was U.S. Senator John Fairfield Dryden. John Kuser later became a New Jersey Republican councilman, assemblyman, and state senator. They also lived in Bernardsville, New Jersey.

Brooke described her tumultuous first marriage as the “Worst years of my life”, which was punctuated by her husband’s alleged physical abuse, alcoholism, and adultery. According to Frances Kiernan’s 2007 biography of Brooke Astor, when Brooke was six months pregnant with the couple’s only child, her husband broke her jaw during a marital fight. “I learned about terrible manners from the family of my first husband,” she told The New York Times. “They didn’t know how to treat people.” A year after the marriage, according to a published account of the divorce proceedings, John “began to embarrass her in social activities” and “told her that he no longer loved her and that their marriage was a failure.”

Brooke and John had one son, Anthony Dryden “Tony” Kuser, May 30, 1924. She filed for divorce February 15, 1930, in Reno, Nevada. It was finalized later that year. John married his second wife, Vieva Marie Fisher Banks (formerly Mrs. James Lenox Banks, Jr.) September 6, 1930, in Virginia City, Nevada. They had one daughter, Suzanne Dryden Kuser, and divorced in October 1935. A week later, Sen. Kuser married Louise Mattei Farry (formerly Mrs. Joseph Farry). In 1958, he married, as his fourth wife, Grace Egglesfield Gibbons (widow of John J. Gibbons). An amateur ornithologist and president of the New Jersey Audubon Society, Sen. Kuser introduced the bill that made the Eastern Goldfinch the state bird of New Jersey. He also was, at various times, an insurance and real estate broker in New Jersey (1937–1942) and Nevada (1942–1955), a vice president of Lenox, Inc., the pottery and china company, a columnist for the Nevada State Journal (1943–1947), and a director of the Fox Film Corporation.

Her second husband, whom she married in 1932, was Charles Henry “Buddy” Marshall (1891–1952). Buddy was the senior partner of the investment firm Butler, Herrick & Marshall, a brother-in-law of the mercantile heir Marshall Field III, and a descendant of James Lenox, the founder of the Lenox Library.  Astor later wrote that the marriage was “a great love match.”

She had two stepchildren by the marriage, Peter Marshall and Helen Huntington Marshall. Helen Marshall’s first marriage was to composer Ernest Schelling[6] and, her second to cellist János Scholz  In 1942, Brooke’s then-18-year-old son Tony changed his name to Anthony Dryden Marshall out of admiration for his stepfather. Buddy’s financial fortunes turned in the mid-1940s, at which time Brooke went to work for eight years as a features editor at House & Garden magazine. She also briefly worked for Ruby Ross Wood, a prominent New York interior decorator who, with her associate Billy Baldwin, decorated the Marshalls’ apartment at 1 Gracie Square in New York City.

In October 1953, eleven months after Charles Marshall’s death, she married her third and final husband, William Vincent Astor (1891–1959), the chairman of the board of Newsweek magazine and the last notably rich American member of the famous Astor family. Vincent was the son of RMS Titanic victim John Jacob “Jack” Astor IV (1864–1912) and socialite Ava Lowle Willing (1868–1958), he had been married and divorced twice before childless and was known to have a difficult personality.  “He had a dreadful childhood, and as a result, had moments of deep melancholy,” Brooke recalled. “But I think I made him happy. That’s what I set out to do. I’d literally dance with the dogs, sing and play the piano, and I would make him laugh, something no one had ever done before. Because of his money, Vincent was very suspicious of people. That’s what I tried to cure him of.”

Not wanting to die alone, Astor agreed to divorce his second wife, Mary Benedict “Minnie” Cushing, only after she had found him a replacement spouse. Minnie had first suggested Janet Newbold Rhinelander-Stewart, the newly divorced wife of James Smith Bush II, who turned down Astor’s proposal with startling candor stating “I don’t even like you”. Minnie then suggested the recently widowed Brooke. Few people believed that the Astor-Marshall union was anything more than a financial transaction. According to Brooke’s friend Louis Auchincloss; “Of course she married Vincent for the money,” adding, “I wouldn’t respect her if she hadn’t. Only a twisted person would have married him for love.”

During her brief marriage to Vincent, whom she called “Captain”, Brooke participated in his real-estate and hotel empire and his philanthropic endeavors. Between 1954 and 1958, she redecorated one of his properties, the Hotel St. Regis, which had been built by his father. Vincent died leaving all his money to Brooke. His younger half-brother socialite John Jacob “Jakey” Astor VI (1912–1992) was left with nothing since Vincent’s hatred for Jakey’s mother Madeleine (Jack’s second wife and widow) led him to believe he was not even a biological Astor. Vincent had nothing but contempt for him. Jakey felt cheated and resentfully stated Vincent “had the legal, not the moral right to keep all the money”. He was certain that Vincent was “mentally incompetent” when signing his last will in June 1958 due to frequent smoking and alcoholism, though Brooke insisted otherwise. While Vincent was hospitalized, Brooke would often bring him liquor. Jakey accused her of using the liquor to influence the will in her favor. Jakey ended up settling for $250,000. The rest of money remained with the Vincent Astor foundation and Brooke. Before Vincent’s death, Brooke once privately admitted to her daughter-in-law Elizabeth Cynthia “Liz” Cryan: “I don’t think I can stand being married to him anymore. I don’t think I can take it. He never wants to go anywhere — he’s so antisocial.”

Though she received several proposals after Astor’s death, she chose not to remarry. In a 1980 interview, she stated: “I’d have to marry a man of a suitable age and somebody who was a somebody, and that’s not easy. Frankly, I think I’m unmarriageable now”, and also said “I’m too used to having things my way. But I still enjoy a flirt now and then.”

Though she was appointed a member of the board of the Astor Foundation soon after her marriage, upon Vincent Astor’s death in 1959, she took charge of all the philanthropies to which he left his fortune. She served as a Trustee of the Metropolitan Museum of Art and chaired the Visiting Committee of the Metropolitan’s Department of Far Eastern Art; she is credited with the idea for a Chinese garden courtyard, the Astor Court, in the Metropolitan. In addition, Astor served as a member of the Metropolitan Museum of Art’s 100th Anniversary Committee and hosted the Metropolitan’s Centennial Ball. Despite liquidating the Vincent Astor Foundation in 1997, she continued to be active in charities and in New York’s social life. The New York Public Library was always one of Astor’s favorite charities, as was The Animal Medical Center. In 1988, she was awarded the National Medal of Arts. She was elected a Fellow of the American Academy of Arts and Sciences in 1992. As a result of her charity work, Astor was awarded the Presidential Medal of Freedom in 1998. Her life’s motto summed up her prodigious generosity: “Money is like manure; it’s not worth a thing unless it’s spread around.”

Among numerous other organizations, she was involved with Lighthouse for the Blind, the Maternity Center Association, the Astor Home for emotionally disturbed children, the International Rescue Committee, the Fresh Air Fund, and the Women’s Auxiliary Board of the Society of New York Hospital.

The Daily News ran a cover story July 26, 2006, describing the family feud between her son Tony and his son Philip Cryan Marshall, regarding Brooke’s welfare.  The story detailed how her grandson, a historic preservationist and associate professor at Roger Williams University, had filed a lawsuit seeking the removal of his father as the socialite’s guardian and the appointment of Annette de la Renta, the wife of designer Oscar de la Renta, instead.

According to accounts published in The New York Times and the Daily News, Astor was diagnosed with Alzheimer’s Disease and suffered from anemia, among other ailments. The lawsuit alleged that Marshall had not provided for his elderly mother and, instead, had allowed her to live in squalor and that he had reduced necessary medication and doctor’s visits, while enriching himself with income from her estate. Philip Marshall further charged that his father sold his grandmother’s favorite Childe Hassam painting in 2002 without her knowledge and with no record as to the whereabouts of the funds received from the sale. In addition to Annette de la Renta, Henry Kissinger and David Rockefeller provided affidavits supporting Philip Marshall’s requests for a change in guardianship.

The day the story appeared, New York Supreme Court Justice John Stackhouse sealed the documents pertaining to the lawsuit and granted an order appointing Annette de la Renta guardian and JPMorgan Chase & Co. to be in charge of Brooke’s finances. Several news organizations including the Associated Press and The New York Times sued to have the records of the Astor case unsealed in the public interest, their request was granted September 1, 2006. Astor was moved to Lenox Hill Hospital, where an unidentified nurse called her appearance “deplorable,” according to the Daily News. Her son Tony unsuccessfully attempted to have his mother transferred to another hospital.

Brooke was released from Lenox Hill Hospital July 29, 2006 and moved to Holly Hill, her 75-acre (30 ha) estate in the village of Briarcliff Manor, New York, where she died August 13, 2007.  In 2008, a book, entitled Mrs. Astor Regrets, by Meryl Gordon, makes use of diaries kept by the nurses who cared for Astor during the last years of her life. The diaries were compiled over the four years Astor received care, and detail the abuse that Mrs. Astor reportedly received from her son, Anthony (Tony).

The New York Times reported August 1, 2006, that Anthony Marshall was accused by Alice Perdue, an employeee in his mother’s business office, of diverting nearly $1 million from his ailing mother’s personal checking accounts into theatrical productions. Marshall, through a spokesman, said that his mother knew of the investments and approved of them. Perdue countered that Marshall had advised her never to send to his mother any documents of a financial nature because “she didn’t understand it.”

The claims made by Philip Marshall regarding his father’s handling of the estate prompted interest into the matter. The New York District Attorney announced indictments on criminal charges against Tony and attorney Francis X. Morrissey Jr., November 27, 2007. The charges stemmed from the district attorney’s office and subsequent grand jury investigation into the mishandling of Astor’s money and a questionable signature on the third amendment to her 2002 will, made in March 2004. That amendment called for Astor’s real estate to be sold and the proceeds added to her residuary estate. An earlier amendment, also made in 2004, which designated Marshall as the executor of his mother’s estate and left him the entirety of the residuary estate, was also under investigation.

The specific charges included grand larceny, criminal possession of stolen property, forgery, scheming to defraud, falsifying business records, offering a false instrument for filing, and conspiracy in plundering her $198 million estate. The most severe charge, grand larceny, carries up to a 25-year sentence.

The trial of Marshall and Morrissey started March 30, 2009, with the jury selection. The judge, Justice A. Kirke Bartley Jr., had originally indicated that the trial could last up to three months. After deliberations that stretched over twelve days and were reportedly marked by bitter disagreements that left one female juror claiming to feel personally threatened, the jury convicted Anthony D. Marshall of one of two charges of grand larceny, the most serious of a number of charges brought against him October 8, 2009. The same jury convicted Francis X. Morrissey Jr. of forgery. In December 2009, Marshall and Morrisey were both sentenced to 1–3 years in prison. Philip C. Marshall, Astor’s grandson, said that now that his father has been convicted in the Brooke Astor will case, he expects the will to be contested by various charities.

November 30, 2011, Sotheby’s announced plans for an April 19, 2012, auction of jewelry as well as fine and decorative arts from her Park Avenue apartment and Holly Hill, her Westchester estate.  Brooke died at age 105, August 13, 2007, from pneumonia at her home in Briarcliff Manor, New York. She is interred in the Sleepy Hollow Cemetery next to Vincent.