The actress plays the agoraphobic Sheila Jackson on the series, which stars William H. Macy as alcoholic father Frank Gallagher.
"I tried doing a sitcom here [in Chicago] and that was an amazing process to experience," the former What about Joan star told TV Squad. "But at that time, sitcoms were really going through an identity crisis, and just doing anything different was really hard.
"Now on cable, it's like you can be totally different and [people] embrace it [and] they want it."
Cusack added that she had no reservations about committing to a television project.
"You're not doing 24 [episodes], you're doing 12 shows, so people can have a life," she insisted. "You're not like a workaholic, insane person avoiding having a life."
She also revealed that she has not watched the UK version of Shameless, which serves as the basis for Showtime's series.
"I thought about watching it because I was curious," she admitted. "But I thought, 'I don't know if that really helps'.
"The nice thing about it is that it's on Showtime, it's John Wells [producing] and it's 12 episodes. That all means that there's room for it to become something [different]."
Shameless continues on Sundays at 10pm on Showtime.