She has also starred as Katie Bowman in USA Network's Colony and Robin Perry in NBC's Council of Dads and has had film roles in Whisper (2007), Black Gold (2011), and The Show (2017).

After graduating from high school, Callies entered Dartmouth College where she obtained a Bachelor of Arts degree in drama in 1999, with a minor in women's studies and a senior fellowship in Indigenous theology.

[1] Callies moved to New York in 2003 and then quickly landed her first television role as Kate O'Malley, a recurring part on the short-lived CBS show Queens Supreme.

After making various guest appearances on Law & Order: Special Victims Unit, Dragnet (2003), and NUMB3RS, Callies gained a starring role on Fox's Prison Break as Sara Tancredi.

According to Prison Break's executive producer Matt Olmstead, although the writers, the network, Callies herself, and he all wanted her to stay on the show, the character was written out due to contract disputes.

"[6] Executive Producer Matt Olmstead admitted the fans' overwhelming response to her death had influenced the decision to bring the character, and Callies, back to the show.

[13] In August 2010, Callies' first screenplay, an adaptation of Campbell Geeslin's children's book Elena's Serenade, was optioned by French production company Fulldawa Films.