The couple will lead the cast of the revival of Neil Simon's marriage comedy "Plaza Suite", which will be directed by Tony Award winner John Benjamin Hickey.
Parker and Broderick last appeared on the Broadway stage together in the 1995 revival of "How to Succeed in Business Without Really Trying".
"I feel I've waited a lifetime," the "Sex and the City" star wrote on Instagram, announcing the production and adding she will be working with someone she gets to "love onstage and off".
"Plaza Suite" is set for a 17-week engagement at the Hudson Theatre, with previews beginning in mid-March (20) and an official opening set for 13 April.
Parker was last on Broadway 22 years ago, when she starred in "Once Upon a Mattress", while Tony winner Broderick last appeared on the New York stage in 2016's "Sylvia".
The "Ferris Bueller's Day Off" star was among the friends and fans who paid tribute to legendary playwright Simon following his death last year.
"It was my great good fortune that my very first Broadway play was written by Neil Simon," he wrote. "He also wrote my first film. I owe him a career."
Broderick and Parker will prepare for the Broadway run of "Plaza Suite" by first taking the play to the Emerson Colonial Theatre in Massachusetts, where the actress made her stage debut in "The Innocents" in 1976.