Van Der Beek started his film career with a supporting role in the teen-oriented movie Angus in 1995. However, he did not gain wide renown until 1998, when he was cast in the lead role of Dawson Leery on the television series Dawson's Creek. He stopped attending college in order to film the series, but plans to return in order to complete his degree.

The series was a big success among its intended teenage audience, and Van Der Beek became a well known teen idol. His on and off air chemistry with Katie Holmes was one of the main reasons for the success of the show. Although during the first season of the show, James and Katie were dating.

In 1999, Van Der Beek took a break from Dawson's Creek and starred in the lead role in the film Varsity Blues, as a player on a Texas high school football team. The film was successful, grossing $52 million and Van Der Beek won an MTV award for his lead performance, though the overstated Texas accent he occupied in the film earned him much ridicule in popular culture. He subsequently appeared in "Texas Rangers" and The Rules of Attraction, and also appeared in Standing Still.

In 1998, Van Der Beek was chosen as one of People Magazine's "50 most beautiful people in the world".

Presently, Van Der Beek is working on 2 projects, Eye of the Beast and Zoe (2006) with Eliza Dushku.

In early 2007, he appeared as Tobias Henkel/Raphael, the Unsub, on two episodes of Criminal Minds.