The new season of Scream Queens will pick up about two years after the events of season one, moving from the college campus to a hospital, where some of the most bizarre medical cases are under observation. Stamos will play Dr. Brock Holt, the hospital's "brilliant, but secretive" head surgeon.
See images of John Stamos:
HOLLYWOOD, CA - FEBRUARY 22: John Stamos arrives at the 87th Annual Academy Awards at Hollywood & Highland Center on February 22, 2015 in Hollywood, California. (Photo by Steve Granitz/WireImage)
LOS ANGELES, CA - NOVEMBER 22: Actor John Stamos poses in the press room at the 2005 American Music Awards held at the Shrine Auditorium on November 22, 2005 in Los Angeles, California. (Photo by Vince Bucci/Getty Images)
UNIVERSAL CITY, CA - JANUARY 23: Actor John Stamos of the television show 'Jake in Progress' listens to a question during the ABC 2005 Television Critics Winter Press Tour at the Hilton Universal Hotel on January 23, 2005 in Universal City, California. (Photo by Frederick M. Brown/Getty Images)
BEVERLY HILLS, CA - MARCH 31: Actor John Stamos, arrives at 'A Stellar Night' Gala Honoring actress Dakota Fanning by the Starlight Starbright Children's Foundation held at the Beverly Hilton Hotel, on March 31, 2006 in Beverly Hills, California. (Photo by Frazer Harrison/Getty Images)
NEW YORK - APRIL 18: Actor John Stamos arrives at the A&E Network's 'Up-Fronts' event to unvail its Fall 2006 season line-up at the Time Warner Center's Fredrick P.Rose Hall April 18, 2006 in New York City. (Photo by Clarence Elie-Rivera/Getty Images)
BEVERLY HILLS, CA - JANUARY 15: Actor John Stamos arrives at the NBC/Universal Golden Globe After Party held at the Beverly Hilton on January 15, 2007 in Beverly Hills, California. (Photo by Frazer Harrison/Getty Images)
NEW YORK - FEBRUARY 13: (EXCLUSIVE ACCESS) Actor John Stamos meets with television personality Rachael Ray on the 'Rachael Ray' show on February 13, 2007 in New York City. (Photo by Bryan Bedder/Getty Images)
BURBANK, CA - AUGUST 03: Actor John Stamos arrives to 'Comedy Central Roast Of Bob Saget' at the Warners Brothers Studio Lot on August 3, 2008 in Burbank, California. (Photo by Alberto E. Rodriguez/Getty Images for Comedy Central)
404347 27: Actor John Stamos arrives at the Roundabout Theater Company's 2002 Spring Gala April 22, 2002 in New York City. Plummer received the inaugural Jason Robards Award for contributions to the theater. (Photo by Lawrence Lucier/Getty Images)
NEW YORK - OCTOBER 7: Actor John Stamos joins the cast of 'Nine' with Eartha Kitt at the Eugene O'Neill Theatre October 7, 2003 in New York City. (Photo by Scott Gries/Getty Images)
UNIVERSAL CITY, CA - JANUARY 23: Actor John Stamos arrives at the ABC's Winter Press Tour Party on Wisteria Lane on January 23, 2004 in Universal City, California. (Photo by Vince Bucci/Getty Images)
CULVER CITY, CA - OCTOBER 27: ActorJohn Stamos front row at the Shakti Spring 2005 show at the Mercedes-Benz Fashion Week at Smashbox Studios October 27, 2004 Culver City, California. (Photo by Carlo Allegri/Getty Images)
377853 18: Actress Rebecca Romijn-Stamos kisses her husband John Stamos as they arrive at the 2000 Emmy Awards September 10, 2000 in Los Angeles, CA. (Photo by David McNew/Newsmakers)
HOLLYWOOD, CA - OCTOBER 11: Actor John Stamos attends the Los Angeles Premiere of 'Team America: World Police' at the Grauman's Chinese Theater October 11, 2004 in Hollywood, California. (Photo by Kevin Winter/Getty Images)
FULL HOUSE - Cast Gallery - July 1, 1987. (Photo by ABC Photo Archives/ABC via Getty Images)JODIE SWEETIN;BOB SAGET;JOHN STAMOS;DAVE COULIER;CANDACE CAMERON
File Photo of actor John Stamos taken in Los Angeles, Calif. on 7/27/84. (Photo by Bob Riha Jr/WireImage)
FULL HOUSE - Cast Gallery - June 26, 1987. (Photo by ABC Photo Archives/ABC via Getty Images)JOHN STAMOS
FULL HOUSE - 'Knock Yourself Out' - Airdate: October 30, 1987. (Photo by ABC Photo Archives/ABC via Getty Images)JOHN STAMOS
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The 52-year-old actor will join returning cast members Jamie Lee Curtis, Emma Roberts, Lea Michele, Abigail Breslin, Keke Palmer, Billie Lourd, Glen Powell and Niecy Nash, who will all reprise their season one characters.
This marks a reunion of sorts for Stamos and Scream Queens creator Ryan Murphy, as he's previously appeared in Glee and The New Normal. It also keeps Stamos in the Fox family after the network canceled his comedy, Grandfathered, in May after just one season.
In March, ET caught up with the cast and producers of Scream Queens at PaleyFest, where co-creator Brad Falchukteased the upcoming season.
"We can expect a lot of very strange patients," Falchuk told ET. "We can expect our characters interacting with them in different and odd ways. We can expect a lot of the same kind of humor, and a lot of the same kind of messaging."
Scream Queens will return Tuesday, Sept. 20 at 9 p.m. ET/PT on Fox.