Wilkins was born in St. Louis, Missouri, in 1901. His mother died when he was four years old, after which Wilkins and his siblings were raised by an aunt and uncle in St. Paul, Minnesota, where they attended local schools. Wilkins graduated from the University of Minnesota with a degree in sociology in 1923. In 1929, he married social worker Aminda “Minnie” Badeau; the couple had no children of their own. The couple did raise the two children of Hazel Wilkins-Colton, a writer from Philadelphia, Pennsylvania.  After graduation, Wilkins worked as a journalist at The Minnesota Daily and became editor of The Appeal, an African-American newspaper. After he graduated he became the editor of The Call.  From 1931-34, Wilkins was assistant NAACP secretary under Walter Francis White. When W. E. B. Du Bois left the organization in 1934, he replaced him as editor of The Crisis, the official magazine of the NAACP. From 1949-50, Wilkins chaired the National Emergency Civil Rights Mobilization, which comprised more than 100 local and national groups.  In 1950, Wilkins—along with A. Philip Randolph, founder of the Brotherhood of Sleeping Car Porters, and Arnold Aronson,[4] a leader of the National Jewish Community Relations Advisory Council—founded the Leadership Conference on Civil Rights (LCCR). LCCR has become the premier civil rights coalition, and has coordinated the national legislative campaign on behalf of every major civil rights law since 1957.

In 1955, Roy Wilkins was chosen to be the executive secretary of the NAACP and in 1964 he became its executive director. He had an excellent reputation as an articulate spokesperson for the civil rights movement. One of his first actions was to provide support to civil rights activists in Mississippi who were being subject to a “credit squeeze” by members of the White Citizens Councils.  Wilkins backed a proposal suggested by Dr. T.R.M. Howard of Mound Bayou, Mississippi, who headed the Regional Council of Negro Leadership, a leading civil rights organization in the state. Under the plan, black businesses and voluntary associations shifted their accounts to the black-owned Tri-State Bank of Memphis, Tennessee. By the end of 1955, about $300,000 had been deposited in Tri-State for this purpose. The money enabled Tri-State to extend loans to credit-worthy blacks who were denied loans by white banks. Wilkins participated in the March on Washington (August 1963) which he helped organize the Selma to Montgomery marches (1965), and the March Against Fear (1966).  He believed in achieving reform by legislative means, testified before many Congressional hearings and conferred with Presidents Kennedy, Johnson, Nixon, Ford, and Carter. Wilkins strongly opposed militancy in the movement for civil rights as represented by the “black power” movement. He was a strong critic of racism in any form regardless of its creed, color, or political motivation, and also declared that violence and racial separation of blacks and whites were not the answer.

However, these moderate views increasingly brought him into conflict with younger, more militant black activists who saw him as an “Uncle Tom”.  Wilkins was also a member of Omega Psi Phi, a fraternity with a civil rights focus, and one of the intercollegiate Greek-letter fraternities established for African Americans.  In 1964, he was awarded the Spingarn Medal from the NAACP.  In 1967, Wilkins was awarded the Presidential Medal of Freedom by Lyndon Johnson. During his tenure, the NAACP played a pivotal role in leading the nation into the Civil Rights movement and spearheaded the efforts that led to significant civil rights victories, including Brown v. Board of Education, the Civil Rights Act of 1964, and the Voting Rights Act of 1965.  In 1968, Wilkins also served as chair of the U.S. delegation to the International Conference on Human Rights. After turning 70 in 1971, he faced increased calls to step down as NAACP chief. In 1976, he fell into a dispute with undisclosed board members at the NAACP national convention in Memphis, Tennessee. Although he had intended to retire that year, he decided to postpone it until 1977 because he thought that the pension plan offered to him by the NAACP was inadequate. Board member Emmitt Douglas of Louisiana demanded that Wilkins disclose the offenders and not impugn the board as a whole. Wilkins merely said that the offenders had “vilified” his reputation and questioned his health and integrity.  In 1977, at the age of 76, Wilkins finally retired from the NAACP and was succeeded by Benjamin Hooks. He was honored with the title Director Emeritus of the NAACP in the same year. Roy Wilkins died on September 8, 1981 in New York City of heart problems related to a pacemaker implanted on him in 1979 due to his irregular heartbeat. In 1982, his autobiography Standing Fast: The Autobiography of Roy Wilkins was published posthumously.  The players in this drama of frustration and indignity are not commas or semicolons in a legislative thesis; they are people, human beings, citizens of the United States of America.

Wilkins was a staunch liberal and proponent of American values during the Cold War, and denounced suspected and actual communists within the civil rights movement. He has been criticized by some, on the left of the civil rights movement, such as Daisy Bates, Paul Robeson, W. E. B. Du Bois, Robert F. Williams, and Fred Shuttlesworth, for his cautious approach, his suspicion of grassroots organizations, and his conciliatory attitude towards white anticommunism.  In 1951, J. Edgar Hoover and the state department, in collusion with the NAACP and Wilkins (then editor of The Crisis, the official magazine of the NAACP), arranged for a ghost-written leaflet to be printed and distributed in Africa.  The finished article published by the NAACP was called Paul Robeson: Lost Shepherd, penned under the false name of “Robert Alan”, whom the NAACP claimed was a “well known New York journalist.” Another article by Roy Wilkins, called “Stalin’s Greatest Defeat”, denounced Robeson as well as the Communist Party of the USA in terms consistent with the FBI’s information. At the time of Robeson’s widely misquoted declaration at The Paris Peace Conference in 1949, that African Americans would not support the United States in a war with the Soviet Union because of their continued lynchings and second-class citizen status under law following World War II, Roy Wilkins stated that regardless of the number of lynchings that were occurring or would occur, Black America would always serve in the armed forces. Wilkins also threatened to cancel a charter of an NAACP youth group in 1952 if they did not cancel their planned Robeson concert.