The entertainers first appeared together in 1979 in their Tony Award-winning performances in the musical "Evita."
Their latest venture is to play at Manhattan's Barrymore Theatre, starting Nov. 16 and running through Jan. 13. Opening night is set for Nov. 21.
The Broadway premiere follows appearances across the United States, in Toronto, Australia and New Zealand.
Producers describe the show in a synopsis as "a funny, passionate, intimate and unique musical love story told entirely through a masterful selection of some of the greatest songs ever written for the stage."
"I so adore working with Mandy," LuPone said in a statement this week. "He's always been a risk taker, a quality I love best in an actor. I treasure our partnership which began in 'Evita' and which today is stronger than ever. And that's rare."
"To be onstage with Patti is as good as it gets for me," added Patinkin. "When I look into her eyes, I'm 30 years younger instantly. We're right back in time and I'm just in heaven. I'm only sad when the evening's over."