Dominczyk moved with her family from Kielce in Poland to New York City when she was seven, after her parents were expelled from their native Poland for her father's involvement with Amnesty International and then the Solidarity movement. In New York she lived near the Glenwood projects in Canarsie. [citation needed] Dominczyk majored in drama at Carnegie Mellon University and graduated in 1998. She got her big break on Broadway in 1999 as Anna Friel's understudy in Patrick Marber's production of Closer and appeared in the 2003 Broadway production of Enchanted April.

Dominczyk is perhaps best known for her role as Edmond Dantès' beautiful fiancee Mercedes in the 2002 screen adaptation of The Count of Monte Cristo. She has also played small parts in 24, Rock Star (2001), Kinsey (2004), and a more prominent role in the made-for-TV movie The Five People You Meet in Heaven (2004). She co-starred in the 2003 thriller Tough Luck. She has also worked in theatre, appearing alongside Luke Mably in the West End stage adaptation of the Lars von Trier film Festern (a.k.a. The Celebration).

In June 2005, Dominczyk married actor Patrick Wilson who starred in HBO's adaptation of Angels in America, the feature film The Alamo (2004), The Phantom of the Opera, and Hard Candy, as well as a number of Broadway productions. On June 23, 2006, she gave birth to their son, Kalin Patrick Wilson.

In addition to being fluent in English and her native Polish, Dominczyk is semi-fluent in Spanish and French.