David Arquette made his debut in the American drama series ‘The Outsiders’ in 1990. The series lasted for 13 episodes. He made his first big-screen appearance in the 1992 crime drama neo-noir thriller film ‘Where the Day Takes You,’ directed by Marc Rocco. Despite receiving positive reviews from critics, the film tanked at the box office. That same year, he also appeared in the comedy horror film ‘Buffy the Vampire Slayer,’ directed by Fran Rubel Kuzui. The film opened to mixed reviews but failed to garner much success at the box office. He next appeared in ‘Grey Knight’ (1993), ‘Roadracers’ (1994), ‘Airheads’ (1994), ‘Fall Time’ (1995), and ‘Wild Bill’ (1995).
In 1996, he starred as ‘Bobby Conway’ in the American romantic comedy-drama film ‘Beautiful Girls.’ The film received positive response from critics and earned an approval rating of 79% on Rotten Tomatoes. That same year, he was seen playing the role of ‘Deputy Dewey Riley’ in the American slasher film ‘Scream,’ directed by Wes Craven. The film earned praise from critics and was a phenomenal box office success, grossing over $173 million against a budget of $14–15 million. In 1997, he reprised his role as ‘Deputy Dewey Riley’ in ‘Scream 2,’ the sequel to the 1996 film ‘Scream.’ The film opened to critical acclaim and was a major commercial success. Arquette played the role of ‘Rob Geller’ in the romantic comedy film ‘Never Been Kissed,’ directed by Raja Gosnell. The film received mostly positive reviews and did well at the box office.
In ‘Scream 3,’ the third installment in the Scream franchise, Arquette returned to play ‘Deputy Dewey Riley.’ The film opened to mixed reception which was lower than the previous films which had received positive reviews. Despite this, the film was a major financial success. Arquette also won the ‘Blockbuster Entertainment Award’ and ‘Teen Choice Award’ for his performance in the film. He next appeared in ‘3000 Miles to Graceland’ (2001), ‘The Grey Zone’ (2001), ‘It's a Very Merry Muppet Christmas Movie’ (2002), ‘Stealing Sinatra’ (2003), ‘Never Die Alone’ (2004), ‘The Adventures of Sharkboy and Lavagirl in 3-D’ (2005), ‘The Darwin Awards’ (2006), ‘Hamlet 2’ (2008), and ‘Scream 4’ (2011).
In 2014, he portrayed ‘Capt. Henry DuPont’ in the war drama film ‘Field of Lost Shoes,’ directed by Sean McNamara. The film received negative reviews with critics lambasting the movie for its misleading depiction of Southern attitude toward slavery. In 2017, he starred as ‘Diesel Stone’ in the American action comedy film ‘Once Upon a Time in Venice,’ directed by Mark Cullen. The film was panned by critics and tanked at the box office. In 2022, Arquette acted in the slasher film ‘Scream,’ directed by Matt Bettinelli-Olpin and Tyler Gillett. The film received mixed response from critics.