In 1978, she moved to Los Angeles, where she studied drama at the Lee Strasberg Theatre and Film Institute and became a member of the improvisational comedy troupe The Groundlings.

In the 1990s, Griffin began performing as a stand-up comedian and appeared as a guest star on television shows, including a supporting role on the NBC sitcom Suddenly Susan (1996–2000).

[3] Griffin is known for her controversial style and statements about celebrities, religion and sexuality, including holding a mask stylized as Donald Trump's severed head in 2017, which provoked a United States Secret Service investigation and later became the basis of her concert film A Hell of a Story (2019).

[7] Griffin's eldest brother Kenny was a drug addict and homeless at various times; she said she was "afraid of him until the moment he died" because of his violent, abusive nature.

[8] At elementary school, Griffin began to develop a dislike for organized religion because of the punishments she and other "vulnerable" students received from the nuns.

[7] At her high school, she sought refuge in musical theater, playing roles such as Rosemary in How to Succeed in Business Without Really Trying and Hodel in Fiddler on the Roof.

With Janeane Garofalo, she created a standup act called "Hot Cup of Talk", which became the title of her 1998 solo HBO special.

Griffin twice appeared as Susan Klein, a reporter on NBC's The Fresh Prince of Bel-Air; it was her television sitcom debut.

Canada A-List Awards, which included a parody of the "wardrobe malfunction" experienced by Janet Jackson in the Super Bowl halftime show in 2004.

A week prior, she released her second comedy album Suckin' It for the Holidays; it was her second bid to win a Grammy Award.

[21] Griffin has also guest-starred in a 2009 episode of Law & Order: Special Victims Unit, playing a lesbian activist.

[22] Since the 2008 presidential election, Griffin has made frequent jokes about Republican vice-presidential contender Sarah Palin and her family.

[24] On January 7, 2012, it was announced that Griffin would host a weekly one-hour talk show on the channel Kathy, which would consist of standup routines, "rant about pop culture", and celebrity interviews.

According to FOX 411, Bravo was planning to film several comedy specials starring Griffin after the show ended.

[30][31] She declined to discuss the ban on Access Hollywood[32] As of August 2009, Griffin had been un-banned from The View and was a guest on September 18, 2009, and June 15, 2010.

[39] The second season of My Life on the D-List, which premiered June 2006, earned Griffin the 2007 Primetime Emmy for Outstanding Reality Program in non-competition.

[43] In a July 2009 episode of My Life on the D-List, Griffin used profanity in an Octomom joke during her routine at New York's Apollo Theater.

[44] On May 30, 2017, Griffin posted a video of herself holding "a mask styled to look like the severed, bloody head" of then U.S. President Donald Trump.

[48][49] On June 2, 2017, Lisa Bloom, an attorney for Griffin stated, "Like many edgy works of artistic expression, the photo could be interpreted different ways.

[60][61] On November 4, 2020 (her 60th birthday and the day after the 2020 United States presidential election), Griffin once again posted a photo of herself with a model of Donald Trump's bloody, severed head.

Musk tweeted the same day that anyone impersonating a public figure would be permanently suspended unless the account was clearly marked as parody.

She said; "I may have been into The Brady Bunch like every other kid, but I also wanted to watch John Lennon and Yoko Ono on The Dick Cavett Show, and every minute of the Watergate hearings.

"[67] She has also named her mother Maggie as influential in her consumption of pop culture, calling her "the ideal audience for the Hollywood dish".

Griffin named the character Rhoda Morgenstern of 1970s sitcom The Mary Tyler Moore Show as an influence.

She portrays herself as a Hollywood outsider and has a group of close celebrity friends such as Rosie O'Donnell, Joan Rivers, Jerry Seinfeld, Gloria Estefan, and Lance Bass.

[70][71] In 2007, Griffin commented on her aversion to making fun of celebrity friends; "There's nothing I won't do, but on the other hand I'm full of shit because that changes".

Griffin held meetings with several Members of Congress to encourage its repeal; she also organized a rally in Freedom Plaza.

Wozniak and Griffin served as King and Queen of the Humane Society of Silicon Valley Fur Ball on April 5, 2008, in Santa Clara, California.

[110] On August 9, 2009, Griffin attended the Teen Choice Awards with Levi Johnston[111] and then interviewed him on Larry King Live.

[112] On March 7, 2011, while appearing on The Howard Stern Show, Griffin announced that she was romantically involved with actor and former NFL practice-squad player Isaiah Mustafa.