The Oscar-nominated actress will appear in all 12 episodes of the drama, Showtime announced today.
She will play Sheila, an agoraphobic housewife in Chicago with a difficult teenage daughter. Sheila eventually becomes friends with Frank Gallagher (William H Macy).
The role was played by Maggie O'Neill in the British version of the show.
The American Shameless also stars Emmy Rossum, Justin Chatwin, Ethan Cutkosky, Shanola Hampton, Steve Howey, Emma Kenney, Cameron Monaghan, Jeremy Allen White and Laura Slade Wiggins.
The series will go into production next month and is expected to premiere on Showtime on January 9.