[6] Lake made her film debut as Tracy Turnblad, the lead character in John Waters' 1988 cult classic Hairspray.

[7] Lake also starred in other Waters films including Cry-Baby (with Johnny Depp and Susan Tyrrell), Cecil B. Demented (with Melanie Griffith and Stephen Dorff), and Serial Mom (with Kathleen Turner and Sam Waterston).

She starred in Mrs. Winterbourne with Shirley MacLaine and Brendan Fraser, Cabin Boy, Last Exit to Brooklyn, Cookie, and Inside Monkey Zetterland.

She joined the cast of the Vietnam War drama series China Beach as a Red Cross volunteer, Holly "the Donut Dolly" Pelegrino, for the show's third season.

She had a cameo appearance in the 2007 remake of the original cult-classic Hairspray as a William Morris talent agent, and teamed up with star Nikki Blonsky (who played Tracy Turnblad in the 2007 movie musical remake) and Marissa Jaret Winokur (who played Tracy Turnblad in the Broadway musical based on the original 1988 film) to record "Mama I'm a Big Girl Now" for the soundtrack.

Although Sony Pictures Television had many stations contracted through the 2004–2005 season, Lake decided to end the show in August 2004, citing (among other things) a desire to spend time with her family.

Ricki Lake is a talk show host known for discussing controversial psychological topics, including those related to family dynamics and the impact of trauma on parent-child relationships.

[12] She also signed a development deal with Gameshow Marathon production company FremantleMedia for other ventures, including creating and producing future programs and projects.

[15] The Business of Being Born included footage and details of Lake's own "life-changing" home-birthing experience and followed a midwife going about her work.

[15] Lake described it as her life's work for the last three years and expressed hopes that the film educated and empowered people to really know their choices in childbirth.

[17] Lake and Epstein also launched MyBestBirth.com, an online social network, powered by Ning, intended to allow parents and medical professionals to dialogue about varying birthing options and resources.

[18][19] On November 10, 2010, Lake joined fellow talkers Phil Donahue, Sally Jessy Raphael, Geraldo Rivera, and Montel Williams as guests of Oprah Winfrey on The Oprah Winfrey Show, marking the first time those hosts appeared together on one show since their respective programs left the air.

After making the finals, Lake was announced as the contestant in third place, losing to television personality Rob Kardashian and actor and Army veteran J. R. Martinez, despite having higher scores than either.

[24] On February 11, 2017, Lake appeared as a guest judge on the British talent show Let It Shine with Gary Barlow, Dannii Minogue, and Martin Kemp on the BBC.

In March 2018, at SXSW, Lake and Epstein premiered their documentary film Weed the People, examining the use of cannabis as medicine and its status as a Schedule I prohibited drug in the United States.

[34] Lake has discussed drastic weight changes in interviews, including swings of up to 100 pounds and extreme diets that left her "fainting on, like, the spot.

[49] On January 15, 2011, Lake finished in sixth place in the PokerStars Caribbean Adventure Luxury Ladies Poker Event, collecting $5,587 of the prize pool.

Lake said the struggle had been "debilitating, embarrassing, painful, scary, depressing, lonely," noting that "there have been a few times where I have even felt suicidal over it.