She has appeared in the films Rock Star (2001), The Count of Monte Cristo (2002), Kinsey (2004), Trust the Man (2005), Lonely Hearts (2006), Running with Scissors (2006), Higher Ground (2011), The Letter (2012), The Immigrant (2013), Big Stone Gap (2014), A Woman, a Part (2016), The Assistant (2019), The Lost Daughter (2021), Bottoms (2023), and Priscilla (2023).

[1][2] She moved with her family to New York City in 1983 as asylum seekers due to her parents' political associations (her father's involvement with Amnesty International and the Solidarity movement).

[3] In 1999, Domińczyk made her acting debut on Broadway as Anna Friel's understudy in Patrick Marber's production of Closer.

In 2001, she played Tania Asher in Rock Star,[2] and in 2002, portrayed Edmond Dantès' fiancée, Mercédès Mondego (née Herrera), in the screen adaptation of The Count of Monte Cristo.

[6] Domińczyk had guest starring roles in television series such as Kinsey (2004), 24 (2005), The Bedford Diaries (2006), The Good Wife (2011), Suits (2011), Person of Interest (2012), and Boardwalk Empire (2014).

[7] In 2011, Domińczyk co-starred in Vera Farmiga's directorial debut drama film Higher Ground as a religious group member who develops a brain tumor.