Isabelle was born in Washington, DC but grew up in Atlanta, Georgia. She has one older sister, Madeline, and her parents are Elina and Nick Fuhrman. Her career began when a casting director from Cartoon Network spotted her waiting for her sister and cast her for one of the shows, Cartoon Fridays. Isabelle's first acting gig came in 2006 when she booked a commercial for Rooms to Go furniture, and within a month she was asked to fly to LA to audition for shows. During that time, she scored a bunch of commercial and film roles. Isabelle also appeared in several comedy skits on The Tonight Show with Jay Leno (1992), and shortly thereafter her family moved to Los Angeles so she could further pursue her dream.

Isabelle's big break came when she played Esther in Orphan (2009), which landed her critical acclaim and was hailed as "one of the most momentous examples of acting from a child performer in years." She has won the role of Clove in The Hunger Games (2012), the big-screen adaptation of literary sensation The Hunger Games. That went on to become one of the highest-grossing movies ever with over $407 million at the domestic box office.

Isabelle has been featured in spreads for magazines such as Vanity Fair, Nylon, Marie Claire, Teen Vogue, V, H, Bust and Last magazine.