DeWulf first came into the public spotlight as the star of the 2007 Academy Award winning short film West Bank Story in which she played Fatima, a Palestinian fast food cashier who falls in love with an Israeli soldier.

In May 2009, DeWulf appeared in the Matthew McConaughey Ghosts of Girlfriends Past in which she played Melanie, the Ghost of Girlfriends Present. Her comedic performance received very positive reviews.

Also in 2009, DeWulf starred with Sarah Chalke, Maria Conchita Alonso, Garcelle Beauvais, Gregory Harrison, Judy Greer, and Marla Sokoloff in the Lifetime miniseries Maneater.

DeWulf appeared in the August 2009 comedy The Goods: Live Hard, Sell Hard as Ving Rhames's love interest, and in the 2010 film The Back-Up Plan, with Jennifer Lopez.

She stars in the 2010 film The Taqwacores directed by Eyad Zahra.

She also stars in the 2010 film 41-Year-Old Virgin Who Knocked Up Sarah Marshall and Felt Superbad About It directed by Craig Moss.

Other previous credits for DeWulf include: American Dreamz, The Comebacks, and Ocean's Thirteen. Along with her big screen career, DeWulf has played recurring roles on television's 90210, Girlfriends, and The Hard Times of RJ Berger in addition to guest starring on Chuck, Numb3rs, Reno 911!, and CSI: NY.

In 2007, DeWulf ranked in Maxim magazine’s 'Hot 100' as one of the most desirable women on the planet according to the magazine's readers. In 2009, she was listed in the 'Top 30 under 30' for Nylon magazine.[citation needed] In addition, DeWulf has appeared in pictorials in Zink, Giant, and Complex. She has appeared on the covers of East West Woman and Audrey magazines.