Stamos resumes his previous guest role from last season as Tony Gates, a savvy paramedic and medical student, network officials announced at the Television Critics Association's summer meeting this week.
Paula Malcomson ("Deadwood") will appear in a multi-episode arc as the widow of Gates' dead best friend and war buddy who is a single mother.
Stamos' previous series, "Jake in Progress," was left off ABC's fall schedule.
Field reprises her Emmy-winning role as the bipolar and problematic mother of Dr. Abby Lockhart (Maura Tierney) in the season's second episode.
Braugher ("Homicide: Life on the Street") will appear in a six-episode arc as a carpenter who arrives in the emergency room with a simple cough. But he suffers a stroke while waiting to be seen, and his life eventually falls apart as a result of his paralysis.
Mahoney ("Frasier") will portray a drag queen who wants to assume legal authority for his dying partner's medical care.
"ER" will premiere Sept. 21 with 12 continuous new episodes until its cliffhanger in December. The show will then resume after "The Black Donnellys" completes its first season.