An agent who saw Fischler perform at a Neurotic Young Urbanites production arranged for him to attend an audition for the 1994 action film Speed, which became Fischler's first film acting job. In the film, Fischler played one of the men trapped inside an elevator that nearly falls due to an attack by a bomber.
In 1998, Fischler starred in the independent film The Week That Girl Died, a romantic comedy about three long-time friends in a small New England fishing town. For the part, he received a best lead actor award by the American Film Institute International Film Festival's New Directions jury, which honors independent films. Fischler also appeared in David Lynch's 2001 psychological thriller Mulholland Drive as a man describing a horrible nightmare he had. He also appeared in the 2002 television film Gilda Radner: It's Always Something, a biopic about comedian Gilda Radner, where he played the real-life comedian Eugene Levy. He appeared in the films Twister, Ghost World, and Old School. He was also in The Great Buck Howard. Patrick also played assistant district attorney Ellis Loew in Brian De Palma's 2006 crime film The Black Dahlia. The character was referred to in the film as "Jewboy". Fischler also appeared as a guest star in television shows Angel, Nash Bridges, Burn Notice, Lie to Me, Bones, Cold Case, Monk, Star Trek: Enterprise, Girlfriends, CSI: Crime Scene Investigation, CSI: Miami and CSI: NY. By 2009, he had more than 60 film and television credits.
Fischler appeared in the 2010 comedy film Dinner for Schmucks as Vincenzo, one of the guests at a dinner where rich people bring eccentric guests and compete for who can bring the biggest loser. Fischler also portrayed the real-life gangster Mickey Cohen in the video game L.A. Noir, which was released in May 2011.
Fischler appeared in Red State as ATF Agent Hammond in 2011.
In January 2012, Fischler appeared in One for the Money, a crime thriller film adapted from the 1994 novel of the same name by Janet Evanovich, the first in a series featuring bounty hunter Stephanie Plum. He portrayed Vinnie Plum, a bail bondsman and Stephanie Plum's cousin. He portrayed poet Lew Welch in the 2013 Michael Polish film Big Sur, based on the autobiographical novel by Jack Kerouac. He then played the antagonistic Author on the second half of the fourth season of ABC's Once Upon a Time'. In 2016, he appeared in The Coen brothers' Hail, Caesar!
Recently he was seen as Duncan Todd on the new Twin Peaks.