Leifer's inner-monologue driven, observational style is often autobiographical encompassing subjects about her Jewish ancestry and upbringing, coming out, same-sex marriage, relationships (having been married previously to a man and now partnered with a woman) and parenting.
Leifer was born in East Williston, New York, to an Ashkenazi Jewish family, the daughter of Anna, a psychologist, and Seymour Leifer, an optometrist.
While studying for a theater degree at Binghamton University, Leifer accompanied her then boyfriend Paul Reiser to a comedy club to see him perform at the open mic night at Catch A Rising Star. Later she tried performing at New York's Comic Strip and was introduced by emcee Jerry Seinfeld.
Leifer is a stand-up comedian, writer, producer and actor and has been involved in such television shows as Seinfeld, It's Like, You Know..., Alright Already, and The Larry Sanders Show. With Mitchell Hurwitz, she is the creator of the short-lived The Ellen Show (2001). In 1988, she had her own special on Cinemax titled Carol Doesn't Leifer Anymore, which was produced by David Letterman. This was shortly followed by several more specials, titled Carol Leifer Comedy Cruise (1989), Really Big Show (1990), and Gaudy, Baudy, and Blue (1992). She was a writer on Saturday Night Live during the 1985/1986 season.
She has performed on Late Night with David Letterman 25 times, but has only been on his show once since 1992. Leifer has also appeared on The Tonight Show Starring Johnny Carson, Dr. Katz, Politically Incorrect, Hollywood Squares, Late Night with Conan O'Brien, and The Tonight Show with Jay Leno. Her hosting duties have included four seasons of A&E's Caroline's Comedy Hour, as well as guest stints on Talk Soup and Later. She has written for the Academy Awards for most of the 21st century.
Leifer starred in, created and executive-produced the WB sitcom Alright Already, called one of the "10 Best New Shows of the New Season" by the Los Angeles Times and The Washington Post. Despite good reviews, the show only ran one season.
Her stand-up experience includes opening for Jerry Seinfeld and Frank Sinatra. Sinatra praised Leifer as "one funny broad!" and "I wish my mother had been that funny – I wouldn't have had to work so hard." She continues working the stand-up circuit and is reportedly writing an original picture for DreamWorks. Additionally, Leifer is a writer and co-executive producer on the CBS sitcom Rules of Engagement.
On September 14, 2007, Leifer won an auction for the handwritten notes used by Michael Vick during his apology for his role in dogfighting.
Leifer began filming as a contestant for the third season of Celebrity Apprentice in October 2009. However, she was the first to be eliminated on the premiere episode which aired on March 14, 2010.
Leifer joined the Seinfeld writing staff during its fifth season (1993–94), and wrote six episodes for the show between then and its seventh season (1995–96). She has been dubbed "the real Elaine", as the series' character, Elaine Benes, was partially based on her. She has won four Emmy Awards for her work on the series. Her episodes, listed chronologically, are:Season five
"The Lip Reader"
"The Hamptons" (co-written with Peter Mehlman)
"The Secretary" (co-written with Marjorie Gross)
"The Understudy" (co-written with Marjorie Gross)
Lefier has written for several Academy Awards shows, including the 84th Academy Awards in 2012.
Her first book of humorous essays, entitled When You Lie About Your Age, The Terrorists Win was released on March 10, 2009. In it, she discusses the moment she discovered she might be gay and how her life has changed for the better.
From 1981 to 1987, Leifer was married to comic Ritch Shydner, whose gentile status troubled Leifer's father.
In 1996, Leifer met Lori Wolf, a Jewish real estate executive, when they shared a table at a Project Angel Food charity dinner in Los Angeles. Although Leifer had identified as heterosexual up until then, she later contacted Wolf through the host of their table, though Wolf initially rebuffed Leifer's overtures because Wolf was in a relationship at the time. Wolf contacted Leifer weeks later, after Wolf had ended her relationship, and began one with Leifer. They moved in together in 2005, and in acclimating herself to Wolf's pets, Leifer became an animal rights activist. It was for this reason that she chose North Shore Animal League as her charity when she appeared in The Celebrity Apprentice. In 2006 they purchased a $3.2-million, 5,000-square-foot (460 m2) home in the Santa Monica Hills, as part of their preparations to adopt their nine-month-old son, Bruno Leifer-Wolf, who was born in Guatemala in 2007. That year, Leifer proposed to Wolf over dinner at the Palm Restaurant in Beverly Hills. On December 5, 2015, they were married by Rabbi Ron Stern at the Brentwood Country Club in Los Angeles. In attendance were Jane Lynch, Larry David, Bill Maher, Garry Shandling, Henry Winkler, Larry Miller, Jay Leno and Paul Reiser.
Leifer has become vegan, saying "I recently became vegan because I felt that as a Jewish lesbian, I wasn’t part of a small enough minority. So now I’m a Jewish lesbian vegan."