He is known for his portrayals of Pacey Witter on The WB's teen drama Dawson's Creek (1998–2003), Peter Bishop in the Fox science fiction series Fringe (2008–2013), a troubled married man on Showtime's The Affair (2014–2018), and Christopher Duntsch in the Peacock crime drama series Dr. Death (2021).

His other film appearances include Apt Pupil (1998), Urban Legend (1998), Cruel Intentions (1999), The Skulls (2000), Gossip (2000), The Safety of Objects (2001), The Laramie Project (2002), Cursed (2005), Bobby (2006), and Shutter (2008).

[5][6] Jackson lived in California until the age of 8 when he moved to Vancouver with his mother and younger sister; he has said that his father was a bad parent and husband and abandoned the family when they were in the U.S.

[8] Soon after, he landed the role of Charlie (#96) in The Mighty Ducks series, playing a young and aspiring hockey player.

Jackson went on to appear as Pacey Witter on Dawson's Creek, which was created by Kevin Williamson and ran on the WB network from 1998 to 2003, and also starred James Van Der Beek, Michelle Williams, and Katie Holmes.

[9] While the show was on hiatus, he appeared in several movies including Cruel Intentions (an adaptation of Les Liaisons dangereuses that also starred Sarah Michelle Gellar and Ryan Phillippe), The Skulls, The Safety of Objects, The Laramie Project and a short cameo in the remake of Ocean's Eleven in which he appears as himself in a poker scene with Brad Pitt, George Clooney and Holly Marie Combs.

[10] He also was cast as "Beau" in the movie Gossip in 2000 with actors James Marsden, Kate Hudson and Norman Reedus.

Shortly after Dawson's Creek ended in 2003, Jackson played the lead role in films alongside Dennis Hopper (Americano), Harvey Keitel (Shadows in the Sun), and Donald Sutherland (Aurora Borealis).

In 2005, Jackson moved to the UK and made his stage debut on the London West End with Patrick Stewart in David Mamet's two-man play, A Life in the Theatre.

[11][12] From 2008 to 2013, Jackson played the lead role of Peter Bishop in the science-fiction series Fringe,[13] created by J. J. Abrams, Roberto Orci and Alex Kurtzman.

Footage of the event was recorded for a video, entitled 'Pacey-Con', which he was filming for Will Ferrell's Funny or Die celebrity humor website.

[26] Jackson was cast as Dr. Christopher Duntsch, a neurosurgeon who was convicted of intentionally maiming his patient, in Dr. Death which was based on the podcast of the same name, replacing Jamie Dornan.