While working toward a career in roofing, Mewes made his film debut in Smith's 1994 film Clerks as Jay. The film was a huge success resulting in Mewes becoming closely identified with the role, which he also played in Mallrats (1995), Chasing Amy (1997), Dogma (1999), Jay and Silent Bob Strike Back (2001), Clerks II (2006) and the upcoming sequels Mallrats 2 (2016) and Clerks III (TBA). He also supplied Jay's voice in the short-lived Clerks: The Animated Series. He, along with Kevin Smith, performed in the films Scream 3 and Bottoms Up and on Canadian television series Degrassi: The Next Generation. He appeared in two episodes of a three-part story arc in which he and Smith film a new addition to Smith's View Askew films titled Jay and Silent Bob Go Canadian, Eh? at Degrassi Community School. They appear again on Degrassi (in a two-part episode), at the premiere of Jay and Silent Bob go Canadian, Eh? in Canada. Mewes, Smith, and Degrassi star Stacie Mistysyn made the cover of the January 29, 2005 issue of Canadian TV Guide.