Inspired by his parents' work in comedy and show business, a 17-year-old Shore made his stand-up debut at the Alley Cat Bistro in Culver City. "Everyone else in school was filling out their SAT applications, but I just passed mine back. I knew I wasn't going to go to college." Shore was mentored by Sam Kinison and opened several of his sets. While touring the comedy club circuit, Shore cultivated an alter ego persona called "The Weasel".
"The Weasel" involved Shore speaking in a surfer parlance, heavily peppered with dudespeak slang such as "edged", "melons" and "grinding" as well as his catchphrase, "Hey, BU-DDY."
Shore's big break came as an on-air MTV VJ, a position he held from 1989 to 1994. At the height of his MTV fame, Shore had his own show, Totally Pauly, serving as a host on MTV's annual Spring Break parties. He also released a music video, "Lisa, Lisa, the One I Adore".
In 1992, Shore starred in Encino Man, which was a modest hit. The film's success propelled Shore to star in additional personalized vehicles, albeit increasingly less successful: Son in Law (1993), In the Army Now (1994), Jury Duty (1995), and Bio-Dome (1996). All five films received sharply negative reviews, with the last three each holding a rating below 10% at Rotten Tomatoes; in addition, each of the movies grossed less at the box office than the one before. In 1997, Shore starred in the eponymous TV show Pauly; the show was cancelled after five episodes aired. Shore makes a cameo appearance in the American rock band Limp Bizkit music video "N 2 Gether Now", as a pizza deliveryman, and a briefer appearance in "Break Stuff".
In 2003, Shore produced, wrote, directed and starred in Pauly Shore Is Dead, a semi-autobiographical mockumentary, which gave him the best reviews of his career (57% on Rotten Tomatoes, far above his 1990s films), and in 2005, starred in the short-lived reality television series Minding the Store. In 2010, Shore starred in Adopted, which sees him traveling to Africa to adopt a child.