Hemsley was born and raised around 22nd and Christian streets in South Philadelphia by his mother, who worked in a lamp factory. He did not meet his father until he was 14. He attended Barrat Middle School, Central High School for 9th grade and Bok Technical High School for 10th, when he dropped out of school and joined the United States Air Force, where he served for four years. On leaving the Air Force, he returned to Philadelphia, where he worked for the Post Office during the day while attending the Academy of Dramatic Arts at night. He then moved to New York, continuing to work for the Post Office during the day while working as an actor at night. He starred as the character Gitlow in the early 1970s Broadway play Purlie.

Sherman Hemsley performed with local groups in Philadelphia before moving to New York to study with Lloyd Richards at the Negro Ensemble Company. Shortly after, he joined Vinnette Carroll’s Urban Arts Company appearing in these productions: But Never Jam Today, The Lottery, Old Judge Mose is Dead, Moon on a Rainbow Shawl, Step Lively Boys, Croesus, and The Witch. He made his Broadway debut in Purlie and toured with the show for a year. In the summer of 1972 he joined the Vinnette Carroll musical Don’t Bother Me, I Can’t Cope ensemble in Toronto, followed a month later in the American Conservatory Theater production at the Geary Theater. In this his production Hemsley performed the solos “Lookin’ Over From Your Side” in Act I and “Sermon” in Act II.

While Hemsley was on Broadway with Purlie, Norman Lear called him in 1971 to play the role of George Jefferson in his new sitcom, All in the Family. Hemsley was reluctant to leave his theatre role, but Lear told him that he would hold the role open for him. Hemsley joined the cast two years later. The characters of Hemsley and co-star Isabel Sanford were supporting roles on All in the Family, but were given their own spin-off, The Jeffersons, less than two years after Hemsley made his debut on the show. The Jeffersons proved to be one of Lear’s most successful shows, enjoying a run of 11 seasons through 1985.

Hemsley continued to work steadily after the show’s cancellation, largely typecast in George Jefferson–like roles. He teamed up with the show’s original cast members when The Jeffersons moved to Broadway for a brief period.  Hemsley joined the cast of NBC’s Amen in 1986 as Deacon Ernest Frye, an unscrupulous church deacon. The show enjoyed a run of five seasons, ending in 1991. Hemsley then was a voice actor in the ABC live-action puppet series Dinosaurs, where he played Bradley P. Richfield, main character Earl’s sadistic boss. The show ran four seasons, ending in 1994.

Hemsley retired from television acting, although he and Isabel Sanford appeared together in the mid- to late-1990s and in the early 2000s, reprising their roles in guest spots on such television programs as The Fresh Prince of Bel-Air, in commercials for The Gap, Old Navy and Denny’s, and at dry cleaning conventions. He also starred with Sanford in a touring company of “The Real Live Jeffersons” stage show in the 1990s. He and Sanford also made a cameo appearance in the film Sprung. They continued to work together on occasion until Sanford began having the health problems that led to her death in 2004.

Hemsley made three appearances in the sitcom Sister, Sister as Ray Campbell’s father. He also made a voice appearance as himself in the Seth MacFarlane animated comedy Family Guy. He appeared in the film American Pie Presents: The Book of Love. In 2011, he reprised his role as George Jefferson once again, along with Marla Gibbs as Florence Johnston on Tyler Perry’s House of Payne.  He was inducted into the Television Academy Hall of Fame in 2012.

In 1989 Hemsley, who had previously been a jazz keyboardist, released a single titled “Ain’t That a Kick in the Head.” This was followed in 1992 with Dance, an album of rhythm and blues music. He appeared on Soul Train around the time of the record’s release and also performed the song “Eyes in the Dark.”  Hemsley was a fan of 1970s progressive rock bands, including Yes, Gentle Giant, Gong, and Nektar. In 1999 Hemsley collaborated with Yes lead singer Jon Anderson on an album titled Festival of Dreams which was not released.

Hemsley was a shy and intensely private man who was characterized by some as reclusive. He avoided the Hollywood limelight and little of his personal life was public knowledge beyond the facts that he never married and had no children. In 2003, however, Hemsley granted a rare video interview to the Archive of American Television. “It [playing George Jefferson] was hard for me. But he was the character. I had to do it.”  On July 24, 2012, Hemsley died at his home in El Paso, Texas. He was 74 years old. The cause of death was a result of a cancerous mass on his lung, according to the El Paso County Texas Medical Examiner.

On August 28, 2012, an El Paso news anchor interviewed Flora Isela Enchinton, the sole beneficiary of Hemsley’s will, who said they were friends and had been his business partner and manager for more than two decades. During this time she lived with Hemsley and Hemsley’s friend Kenny Johnston. Enchinton told the Associated Press Hemsley never mentioned any relatives. “Some people come out of the woodwork—they think Sherman, they think money,” Enchinton tells AP. “But the fact is that I did not know Sherman when he was in the limelight. I met them when they [Hemsley and Johnston] came running from Los Angeles with not one penny, when there was nothing but struggle.”

A Philadelphia man named Richard Thornton claimed to be the brother of Hemsley and the true heir to his estate. After contesting a June 17, 2012, will, Thornton halted progress on funeral arrangements, and as a result, Hemsley’s body remained refrigerated in the San Jose Funeral Home in El Paso and unburied for months. On November 9, 2012, the legal battle over Hemsley’s body ended when Judge Patricia Chew ruled in favor of Enchinton.  A military funeral was planned for Hemsley. He was interred at Fort Bliss National Cemetery in his adopted hometown of El Paso, Texas.