Beginning in high school and throughout college, Menzel often played and sang at weddings. Her professional life changed greatly when she auditioned for a rock musical based upon Puccini's La Bohème. That show, the late Jonathan Larson's Rent, was Menzel's Broadway debut. For her performance as Maureen Johnson in the original cast of the 1996 musical she received a Tony nomination in the Best Featured Actress in a Musical category. It was also during her time in Rent that Menzel met her future husband, actor Taye Diggs, who was playing the role of Benny. The two were married on January 11, 2003. While the two currently have no children, they do have a pet dog named Sammy Davis Jr..

Following the success of Rent, she originated the role of Dorothy in Summer of ’42 at Goodspeed Opera House in Connecticut, starred as Sheila in the Broadway Encores! Production of Hair and appeared on Broadway as Amneris in Aida. Menzel earned a Drama Desk Award nomination for her performance as Kate in the Manhattan Theatre Club's 2000 off-Broadway production of Andrew Lippa's The Wild Party. Her other off-Broadway credits include Rent and The Vagina Monologues.

Menzel appeared on Broadway in Wicked, the musical by Stephen Schwartz and Winnie Holzman that was based upon the popular 1995 Gregory Maguire novel. While in this musical, she received the 2004 Tony Award for Best Leading Actress in a Musical for her portrayal of Elphaba, the Wicked Witch of the West. During a matinee performance of Wicked on January 8, 2005, she fell through a trap door and cracked a lower rib. The January 8 show was supposed to be her second-to-last performance of Wicked, but the injury prevented her from performing in the January 9 show, which was supposed to be her final performance. However, Menzel did make a special out-of-costume appearance on January 9 and did her final song to a standing ovation before being bid farewell at the curtain call.

Menzel recently appeared off-Broadway in the Public Theater's production of See What I Wanna See, a controversial new Michael John LaChiusa-penned musical whose run ended in December 2005. For her role as various characters, she received Drama Desk Award and Drama League Award nominations.

She recently announced she is going to reprise her Tony Award-winning role as Elphaba in the London West End production of Wicked for a "limited season," from September 2006 to the new year.

In film, Menzel has appeared in Summer of Sam, Just a Kiss, Kissing Jessica Stein, Tollbooth, Water, Ask the Dust, and Rent, in which she and five other original cast members reprised their on-stage roles. She also made an appearance in the movie Camp, in which legendary Broadway composer Stephen Sondheim also made a cameo.

Menzel performed at the 1998 Lilith Fair summer concert festival, and continues to write and perform original music. She has toured extensively and frequently performs in various venues throughout New York City. She produced and released her debut album, Still I Can’t Be Still, released on Hollywood Records in 1998. Her sophomore album, Here, was released by Zel Records in 2004. Menzel has contributed to soundtracks, including those for the film The Other Sister and the ABC television dramedy Desperate Housewives.

Singer Ray Charles invited Menzel to be among an elite group of his favorite contemporary artists to duet with him on one of the tracks of Charles' album Genius & Friends. The tracks were recorded in 1998 but were never produced, and it was one of his dying wishes that the album be made, a wish which was fulfilled posthumously.

Menzel has appeared on the cast recordings of Rent and Wicked, two of the best-selling cast recordings, as well as the recordings of Lippa's The Wild Party and LaChiusa's See What I Wanna See, and the soundtrack of the Rent film. She recently signed a record deal with Warner Brothers Records.

Menzel holds a Bachelor of Fine Arts in Drama from New York University's Tisch School of the Arts. Currently, she is filming the movie Enchanted, due in theatres in November 2007.