Oscar nominee replaces Allison Janney in the William H. Macy dramedy
Cusack will appear in all 12 episodes of "Shameless," which will premiere on Sunday, Jan. 9.
"Shameless" is based on the adored British format and features original creator Paul Abbott as executive producer along with Emmy winner John Wells. The series features William H. Macy as the alcoholic patriarch of a working-class Chicago family, but truly stars Emmy Rossum as the eldest daughter who has to keep the family together.
Cusack will play Sheila, an agoraphobic housewife who strikes up a relationship with Macy's character.
The role was played by Allison Janney in the pilot, but with the "West Wing" star committed to ABC's midseason comedy "Mr. Sunshine" and producers determined to expand Sheila into a larger role, there wasn't enough Janney to go around.
Cusack has earned a pair of Oscar nominations for her performances in "Working Girl" and "In & Out." He TV credits include the short-lived "What About Joan" and a run on "Saturday Night Live."
Production on "Shameless" will begin in mid-September.