Also gracing the guest list are Tina Fey, Dustin Hoffman, Jennifer Aniston, Benedict Cumberbatch, Keira Knightley, Julianne Moore, Jake Gyllenhaal, Mark Ruffalo, Octavia Spencer, Ben Stiller, Channing Tatum, Diane Keaton, Robert Duvall, John Travolta and Adam Sandler.
The festival revealed its highly anticipated roster Tuesday as it announced the final slate of films bound for the movie marathon, bringing the total to 285 features and 108 shorts.
New films include St. Vincent, directed by Theodore Melfi and starring Murray as a retired curmudgeon with a taste for booze and gambling who befriends the 12-year-old son of his next-door neighbour (Melissa McCarthy).
James Franco's The Sound and the Fury, based on the classic William Faulkner novel, will have its North American premiere in Toronto. Franco, who directed and stars in the film, will also attend the fest.
"It's a really strong line-up. We're thrilled with it," said artistic director Cameron Bailey, who touted the festival's international selections as well as its North American films.
"It looks to me like there is as much interest as ever in showing your film in front of a Toronto audience first. The enthusiasm with which we're approached to try to get a slot in Toronto is really remarkable. I hope Torontonians understand just what power they have simply as a film audience in the world."
Scorsese, Schwarzenegger no-shows
Some notable names missing from the list are Martin Scorsese, Arnold Schwarzenegger and Tom Hardy, who all have buzzy movies screening at the fest.
Bailey said Scorsese has not yet confirmed but he is still hopeful the Academy Award-winning director will attend for his collaboration with David Tedeschi, The 50 Year Argument, a documentary tribute to The New York Review of Books.
He added that up-and-coming Quebecois director Xavier Dolan is expected to be at the fest to screen his film Mommy, despite being left off the guest list revealed on Tuesday.
In addition to Franco, several other actors will appear at the fest to promote films they've directed: Alan Rickman for A Little Chaos, the closing night film; Chris Rock for Top Five; Melanie Laurent for Breathe; and Ethan Hawke for his documentary about pianist Seymour Bernstein, Seymour: An Introduction.
Director Antoine Fuqua, meanwhile, will appear with Washington for a public conversation about The Equalizer, their first collaboration since the Academy Award-winning Training Day.
Also participating in onstage discussions as part of the festival's Mavericks program are Witherspoon, Juliette Binoche, Richard Gere, Robert Duvall and The Daily Show host Jon Stewart for his feature-length drama Rosewater.
Rounding out the new films announced Tuesday are Cannes Palme d'Or winner Winter Sleep, Marjane Satrapi's The Voices, starring Ryan Reynolds and Anna Kendrick, and Roger Waters the Wall, a documentary filmed during Waters's recent The Wall Live tour.
143 world premieres
Of the 285 feature films screening at TIFF, 143 are world premieres, nearly on par with last year's 146. Bailey said that a new policy of only screening world and North American premieres during the first four days has not affected the lineup.
"I never was in any doubt that we would have lots of sparkle for people this September," he said. "For us I think this was a question of clarity that we wanted to bring to the selection process and just the scheduling of the films. We've done that and I think the lineup is as strong as ever."
Some buzzed-about films did land elsewhere, including David Fincher's Gone Girl and Paul Thomas Anderson's Inherent Vice, which are opening at the New York Film Festival.
"We never get every film that's out there in the fall and nor could we show them all," said Bailey. "We have to make choices sometimes and sometimes films and film companies make choices of their own as well."
Festival street closed to traffic
Organizers also announced new details of their plans to close King Street West between Peter Street and University Avenue to transform the stretch into "festival Street."
The stretch will become a "pedestrian promenade" that will feature art, food trucks, a "board game concierge" from Toronto bar Snakes & Lattes, musical performances from Rich Aucoin, Jason Collett and Adrian X, a public piano and even a festival therapist.
The festival's Discovery program, which highlights first and second feature films by emerging directors, was also announced Tuesday and will include Ross Katz's Adult Beginners and Sarah Leonor's The Great Man.
Kids and the young at heart can enjoy a handful of newly announced family-friendly films, including Song of the Sea, from Academy Award-nominated director Tomm Moore (The Secret of Kells) and starring Brendan Gleeson and Fionnula Flanagan.
The Toronto International Film Festival runs Sept. 4 to 14 and opens with The Judge, starring Downey Jr. and Duvall.