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She is also known for her talk show, Ricki Lake, which was broadcast internationally from September 1993 until May 2004. When the show debuted, she was 24 and credited as being the youngest person to host a syndicated talk show at the time. In late 2012, Lake began hosting a second syndicated talk show, The Ricki Lake Show. The series was canceled in 2013 after a single season, but Lake won her first Daytime Emmy Award for the project.

She also starred in other Waters films including Cry-Baby, Cecil B. Demented, and Serial Mom. She starred in Mrs. Winterbourne, 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 also had a recurring role on the CBS sitcom The King of Queens as Doug's sister Stephanie. She also had a cameo in the 2007 film Hairspray as a talent agent and sang "Mama I'm A Big Girl Now" with Nikki Blonsky and Marissa Jaret Winokur for the film's end credits.

In 2008, her documentary about home birth and midwifery, The Business of Being Born, was released. She also jointly wrote a book, Your Best Birth, on the world of natural childbirth and birthing options, along with Abby Epstein and Jacques Moritz, which was published in 2009. 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.

She returned to television on May 11, 2009, succeeding Sharon Osbourne as host for the third season of VH1's Charm School. 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.

She competed on the 13th season of Dancing with the Stars. She was partnered with three-time champion Derek Hough and cited Kirstie Alley's appearance as an inspiration to do the show. In October 2019, she began competing in The X Factor: Celebrity.

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. The film focused in particular on the use of cannabis in the treatment of pediatric cancer.