She has made television appearances in True Blood (2008), Manhunt: Unabomber (2017) and The Walking Dead (2021–2022), and is recognized for her roles in films such as X-Men Origins: Wolverine (2009) and John Carter (2012).

[citation needed] She moved to New York City at the age of 17 to enroll at Juilliard School's Drama Division (Group 28: 1995–1999), where she graduated in 1999[9] with a Bachelor of Fine Arts degree.

[8][better source needed] After bit parts that included a stint on the show Haunted and roles in the movies Down with Love, 50 First Dates and 13 Going on 30,[8][better source needed] she gained notice in the film The Merchant of Venice as the female lead Portia, alongside Al Pacino, Joseph Fiennes and Jeremy Irons,[8][better source needed] Collins' audition tape for the supporting role of Jessica having so impressed director Michael Radford that—upon Cate Blanchett's opting out as Portia (due to pregnancy)—Radford had championed Collins becoming Blanchett's replacement.

[10][11] She furthered her profile in 2008 when she was cast as Jason Stackhouse's girlfriend Dawn Green in the first season of the HBO vampire series True Blood, and through a featured role as the hero's love interest Kayla Silverfox in the 2009 X-Men Origins: Wolverine opposite Hugh Jackman.

Her first leading film role came in 2012 when she was cast as the headstrong Martian princess Dejah Thoris in John Carter.