Buzz about the show has been building for months, and it is already a hit, with tickets to the musical sold out through June.
"Spamalot" also looks to be an artistic success, with glowing reviews greeting the opening.
"It seems safe to say that such a good time is being had by so many people (including the cast) at the Shubert Theater that this fitful, eager celebration of inanity will find a large and lucrative audience among those who value the virtues of shrewd idiocy, artful tackiness and wide-eyed impiety," said the New York Times.
Wrote the Washington Post's theater critic: "With 'hit' practically tattooed on its dizzy derriere, Monty Python's "Spamalot" opened last night at the Sam S. Shubert Theatre in a musical production so eager to please that it would, if it could, order you a cocktail and serve you a home-cooked meal."
The show stars Tim Curry, who played transvestite Dr. Frank-N-Furter in "The Rocky Horror Picture Show," David Hyde Pierce, of television's "Frasier," and Hank Azaria, who stars in the Showtime series "Huff."
Director Mike Nichols says it's a very fine theater company.
Also at the opening was original Python member Eric Idle, who penned the story and lyrics for the musical and co-wrote the music with John Du Prez. Idle said adapting the original to the stage was "challenging enough."
The five living members of the original cast — Idle, John Cleese, Terry Gilliam, Terry Jones and Michael Palin — briefly posed for photographs and waved to fans. A sixth member, Graham Chapman, died in 1989.