The drama, which stars America Ferrera in the titular role, suffered a ratings decline of 16% over its third season. The fourth run will play out in a graveyard slot on Fridays between reality series Supernanny and news magazine 20/20.
Unveiling its 2009-10 slate in New York today, the network also confirmed the creation of an all-new comedy block on Wednesday nights. There, it will debut Kelsey Grammer's Hank, Patricia Heaton's The Middle, Courteney Cox's Cougar Town and mockumentary Modern Family.
The much-buzzed about new drama Flash Forward will start Thursday nights, after which Grey's Anatomy and Private Practice are paired.
Lost will return to the schedule for its sixth and final season early in 2010. New seasons of veteran medical comedy Scrubs and returning sitcom Better Off Ted are also being saved for midseason.
Nathan Fillion's crime drama Castle has been picked up for a second season and will air Monday nights after Dancing With The Stars.
On Tuesday, the Dancing results show will serve as lead-in to The Forgotten, a new murder detective drama starring Rupert-Penry Jones and Reiko Aylesworth.
Sunday nights remain unchanged, with Desperate Housewives and Brothers & Sisters returning for their sixth and fourth seasons respectively.
New drama Eastwick, based on the 1987 comedy movie The Witches Of Eastwick, will join the Fall lineup at 10pm on Wednesdays after the comedy block.
Midseason dramas include legal drama The Deep End, murder mystery Happy Town and a new version of cult classic V.
Among the axed and ending shows are veteran comedy According To Jim, Life On Mars, Bryan Fuller's Pushing Daisies, Jonny Lee Miller's Eli Stone and family drama Dirty Sexy Money.
Additionally, ABC confirmed that it would be reinstating quiz show Who Wants To Be A Millionaire? to its primetime lineup over the summer months for a special tenth anniversary run.
> Scorecard: Guide to what's in and out at ABC
> Night By Night: ABC's 2009-10 lineup
> Guide to the new shows in the ABC lineup