Cohn was born in Los Angeles, California, in 1966, and was raised Jewish. She was discovered by Actress Charlotte Rae when Rae and other producers of The Facts of Life visited Westlake School in Bel Air, California, while doing research for the show. Cohn was cast as Natalie Green and portrayed the character for the series' entire run (1979–88), as well as in the reunion movie (2001). Her work on The Facts of Life was honored when she was ranked 43rd on VH1's List of 100 Greatest Kid Stars.

Cohn said that one of the reasons she did The Facts of Life Reunion in 2001 was that the actors in the long-running series have been wrongly denied a cut of the syndication and DVD profits from the series. "We all never got paid and still don't get paid for DVDs and reruns ... we felt we were owed."

In 2003 Cohn was nominated for a Daytime Emmy Award for her work on the TV show What's New, Scooby-Doo?, for which she provided the voice of Velma Dinkley. She reprised her role of Velma on Scooby-Doo! Mystery Incorporated and in several Scooby-Doo movies.

She received a positive notice from Variety for her role in the 2007 Daniel Waters' comedy film Sex and Death 101.

Cohn has continued her acting career outside of The Facts of Life. In 1984 she had a leading role as the daughter alongside Stockard Channing in RKO's video production of "Table Settings". In 1986, she appeared in The Boy Who Could Fly playing the part of Geneva. She also had guest appearances in other popular TV shows, including Charles in Charge (playing Buddy's sister Bunny, a young alcoholic, in the 1988 episode "Bottle Baby"), and two guest appearances in the second season of the cop drama 21 Jump Street (playing Rosa in the 1987 episode "Christmas In Saigon" and the 1988 episode "Chapel of Love"). In 2004 Cohn appeared in the WB comedy The Help. In 2010, Cohn played the role of Violet, the leading character in Casper Andreas's movie Violet Tendencies, and appeared on the Season 8 premiere of TLC's What Not to Wear on October 29, 2010. She appeared in an episode of Hot in Cleveland on July 13, 2011, on The Secret Life of the American Teenager on March 26, 2012, and in The Middle on May 21, 2014.

In 2013, she commented on Charlotte Rae's lobbying on her behalf: "Mr. Reynolds calls me into his office. It seemed that Charlotte Rae had fallen madly in love with me, in part because I reminded her of her best childhood friend Natalie — and I was irrepressible, charming, and hilarious. So she asked the producers to create a part for me in the show. Honestly, the whole thing seemed so fantastic I didn’t know what to think."

After the show, she still remains friends with Rae. Just 2 months before her acting mentor's 90th Birthday in 2016, when Cohn was unavailable to attend The Facts of Life reunion interview, she even bestowed Rae a video message praising her decades-long friend for teaching Cohn the craft of acting.