She starred as Becky in 2006's Clerks II, and mentioned in Back to the Well, the making-of documentary, that the donkey show sequence was what made her decide to take the role. In May of the same year, Dawson, an avid comic book fan, co-created the comic book miniseries Occult Crimes Taskforce. She was at the 2007 Comic-Con to promote the comic. She co-starred with former Rent alum Tracie Thoms in the Quentin Tarantino throwback movie Death Proof in 2007, part of the Tarantino/Robert Rodriguez double feature Grind House. She teamed up with friend Talia Lugacy, whom she met at the Lee Strasberg Academy, to produce and star in Descent. On July 7, 2007, Dawson presented at the American leg of Live Earth.
In 2008, Dawson starred with Will Smith in Seven Pounds and in the Steven Spielberg produced Eagle Eye. Beginning in August, she starred in Gemini Division, an online-based TV series. In the computer animated series Afterworld she voiced the character Officer Delondre Baines. On January 17, 2009, Dawson hosted Saturday Night Live. Later in the year, she voiced the character of Artemis in the animated Wonder Woman film.
In 2009, Dawson performed in The People Speak, a documentary feature film that uses dramatic and musical performances of the letters, diaries, and speeches of everyday Americans, based on historian Howard Zinn's A People's History of the United States.
In 2009, Dawson also voiced the character of Velvet Von Black in Rob Zombie's animated feature, The Haunted World Of El Superbeasto
For the Kasabian album West Ryder Pauper Lunatic Asylum, she is featured singing on the track, "West Ryder Silver Bullet."
In 2010, she starred in the movies Percy Jackson & the Olympians: The Lightning Thief, as Persephone, and Unstoppable, as railway yardmaster Connie.
Dawson appeared at the 2010 MTV VMAs on September 12, 2010.
