Born in Jericho, New York to a Sephardic Jewish American father (whose mother and father came from Greece and Romania, respectively) and a Cuban mother who converted to Judaism, Sigler began acting and singing at the age of seven. In 1999 she was cast as the smart but troubled Meadow Soprano, daughter of New Jersey mob boss Tony Soprano. The show became a success and Sigler rose to some fame as a TV actress.

In 2001, she released a pop album called Here to Heaven, which featured the single Cry Baby. In 2002, she co-authored an autobiography, Wise Girl: What I've Learned About Life, Love, and Loss. She also appeared in Mariah Carey's "Through the Rain" music video.

Sigler then spent five months on Broadway in 2002-2003 playing Belle in the production Beauty and the Beast. She has continued to appear in theatrical roles, such as Rogers and Hammerstein's Cinderella.

In July 2003 she married her agent A.J. DiScala, and took the name Jamie-Lynn DiScala. She has stated that she is a very traditional girl, and never had any doubt that she would take her husband's name after marrying, even professionally. However, in September 2005, Sigler and DiScala announced that they are separating after only two years of marriage, and she subsequently changed her name back.

In 2004, she starred as "Hollywood Madam" Heidi Fleiss in the USA television movie Call Me: The Rise and Fall of Heidi Fleiss. In that same year, she had her first starring feature film role, Extreme Dating, an independent film.

During the early production of The Sopranos, Sigler struggled with an eating disorder and is now a spokesperson for the National Eating Disorders Association. In addition, at age 19 while filming Campfire Stories in Hamburg, New Jersey, she was paralyzed from the waist down for several days having contracted Lyme disease.

Sigler speaks fluent Spanish, having learned it from her maternal Cuban grandmother, who did not speak English.