Born Gilda Susan Radner, on June 28, 1946 in Detroit, Michigan, to Herman and Henrietta Radner. Herman was the owner of a successful upscale hotel, the Seville, where prominent entertainers of the day—including Milton Berle, George Burns, and Frank Sinatra—often stayed. Gilda later described her mother as “aloof” and said that the relationship between them was often strained. But she was very close to her dad.

As a child, Radner was severely overweight and had a speech impediment. Her family spent four months out of every year in Florida, which hindered Gilda from forming enduring friendships. She later attributed her keen sense of humor to these setbacks, as well as to the influence of her live-in nanny, known affectionately as Dibby, who helped to raise Gilda and her older brother, Michael. Dibby, was always there for her, and actually told her to make people laugh about her weight before they had a chance to make fun of her.By high school Gilda had achieved a normal weight due to a diet including appetite suppressants she had been taking since the age of 10, although she had suffered though bulimia.

When she was 12, her father was diagnosed with brain cancer and he died when she was 14. This led to her search for a father figure. Radner attended Liggett High School in Detroit, where she was involved in the drama club and chorus. After graduation in 1964, she enrolled at the University of Michigan, where she stayed for six years, majoring in drama. She dropped out before graduating and moved with her boyfriend to Canada where she landed a job playing a clown on a children’s television show.

In 1972, she made her stage debut in Toronto in a production of Godspell, featuring actors Martin Short, Paul Shaffer, Victor Garber, Eugene Levy, and Andrea Martin. The next year she began performing at Toronto’s Second City comedy club with an improvisational group that included Dan Akroyd and Eugene Levy. She continued appearing in numerous television productions, and in 1973, she made her first film appearance (uncredited) in The Last Detail.

In 1974, Radner left Toronto for New York City, where she joined actor John Belushi (himself an alumni of Second City) and Ackroyd on the National Lampoon Radio Hour. That year she also appeared (uncredited) in Mel Brooks’ Blazing Saddles. Radner was then asked to join producer Lorne Michaels’comedy-sketch television program Saturday Night Live, becoming the first performer signed to the new show. From 1975-1980, she was a regular member with a cast that included Akroyd, Belushi, Chevy Chase, Jane Curtin, Garrett Morris, Laraine Newman, and Bill Murray. While on the show, became its premiere female star. With such characters as Roseanne Roseannadanna, Emily Litella and Baba Wawa, she became America's Sweetheart in the late 1970s. During her tenure on the show, she received three nominations for an Emmy for Outstanding Performance by a Supporting Actress, winning once in 1978.

From her success on Saturday Night Live, in 1979, Radner moved on to Broadway, starring in a one-woman show that she also cowrote, Gilda Radner: Live From New York. That same year she appeared as herself in Mr. Mike's Mondo Video. From 1980-82, she was married to Saturday Night Live guitarist G.E. Smith, during which time Radner starred in the concert film Gilda Live (1980).

In 1982, she teamed up with actor and comedian Gene Wilder for Sidney Poitier’s comedy adventure Hanky Panky (1982). During filming, Radner and Wilder became romantically involved, and following a two-year courtship they married. in France on September 18, 1984. Together they starred in two more feature films: The Woman in Red (1984), and Radner’s last feature film, Haunted Honeymoon (1986). Following production of Haunted Honeymoon, Radner an excessive smoker, became increasingly ill with flu-like symptoms that were ultimately diagnosed as ovarian cancer. She began a long and arduous battle against the disease, which she chronicled in her posthumously-published autobiography, "It's Always Something"(1989). It told about her struggles with the disease, and for which she was posthumously awarded the Grammy for Best Spoken Word or Non-Musical Recording.

Her last appearance was on the HBO TV comedy "It's Garry Shandling's Show" in 1988, playing herself. Radner died in her sleep on May 20, 1989 (which was ironically a Saturday night), in Los Angeles, California. She was 42.

She was survived by her husband, Gene Wilder, and her brother Michael.

Although none of her films were very successful at the box office, Radner is fondly remembered for her zany skits from Saturday Night Live, and as a delightful character actress. After her death, Wilder expanded the support group begun by Radner—Gilda’s Club—into a research center called the Gilda Radner Ovarian Detection Center at Cedars-Sinai Medical Center in Los Angeles.