Patrick Fischler was born in Los Angeles, California, on December 29, 1969. His father, Bill, purchased a restaurant on the Pacific Coast Highway in Santa Monica, when Fischler was five years old, and named it "Patrick's Roadhouse" after him. The restaurant has since become a hotspot for such celebrities as Arnold Schwarzenegger, Sean Penn, Goldie Hawn and Johnny Carson. After graduating from high school, Fischler attended New York University's Tisch School of the Arts, where he met and started dating his Future wife, Actress Lauren Bowles, the half-sister of Actress Julia Louis-Dreyfus. After graduating from Tisch, Fischler and Bowles moved back to Los Angeles, where, along with other New York University graduates, they formed a theater group called Neurotic Young Urbanites. 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.

A graduate of New York University's Tisch School of the Arts, Fischler co-founded the Los Angeles-based theater group Neurotic Young Urbanites. During a performance there, he was approached by an agent to audition for the action film Speed (1994), his first film credit. After guest starring on several television shows, Fischler received increased exposure for his role on Mad Men, for which he based his character in part on entertainer Joey Bishop. Fischler filmed his parts for Lost and Southland simultaneously and, although originally only slated for two Lost episodes, he actually appeared in nine.

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 (1996), Ghost World (2001), and Old School (2003). and The Great Buck Howard (2008), and 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", Film reviewer Stephen Cole called his role in that film "a caricature that is as coarsely anti-Semitic as any sequence in Mel Gibson’s The Passion of the Christ." 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.

Patrick Fischler and Lauren Bowles were married in 2004. They have a daughter named Fia Lucille (born April 2009).

Starting in 2009, Fischler became a recurring cast member on both the ABC drama series Lost and the NBC police drama Southland. He was cast in Lost immediately after the pilot for Southland was filmed and worked on both shows over the course of six months. To do so, he constantly flew back and forth between Hawaii, where Lost is filmed, and Los Angeles, where Southland is filmed, while simultaneously dealing with his wife's pregnancy. Fischler said the Lost producers were "incredibly accommodating" to his schedule. On Southland he played Detective Kenny No-Gun; series creator Ann Biderman described him as a "brilliant, incredibly versatile actor". Although originally expected to appear in only two Lost episodes, he ended up guest starring in nine, appearing in the fifth season as Phil, a member of the Dharma Initiative during a part of the show set in 1977. When he auditions for the role, Fischler did not know the storyline was moving from the present to the past, and did not learn it until he was handed his first script. In a May 2009 interview, Fischler said, "This is not a joke: a year ago if you were to ask me what are the two shows I want to be on, I would have said Mad Men and Lost."

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. In the film, Fischler's character has a pet vulture, which he feeds by chewing food and spitting it directly into the bird's mouth. Fischler also portrayed the real-life gangster Mickey Cohen in the video game L.A. Noire, which was released in May 2011. The game uses a facial performance-capture Technology called MotionScan to record the performances of actors, then convert them to the graphics of the game. The game's casting Directors worked on Mad Men and specifically approached Fischler for the Cohen character, and he accepted because he likes the film noir genre. Fischler said of the experience: "You really get to act in those scenes cause they’re capturing every moment on your face. A slight smile. A small frown. Everything."

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 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!