Hearthrob Jake Gyllenhaal of 'Brokeback Mountain' fame opens the world's oldest competition, which runs from September 2 to 12, with Baltasar Kormakur's 3D mountain thriller "Everest" from Universal, also starring Keira Knightley and Sam Worthington.
Picked to open the season with a bang, the film is based on the true story of the 1996 Mount Everest disaster and is bound to thrill as much as the 2013 festival's hit opener 'Gravity' - though it will have to fight to top the popularity of 2014's opener 'Birdman'.
Festival director Alberto Barbera has fought hard this year, the 72nd edition of the festival, to bring films to Venice before they head to Toronto.
His hopes will be pinned on A-lister Depp gracing the red carpet for 'Black Mass', in which he plays one of the most famous US gangsters.
Director Scott Cooper's biopic depicts the true story of mobster Whitey Bulger and his attempts to take down a rival mafia family by helping out the FBI, and also stars Kevin Bacon, and Britain's Sienna Miller and Benedict Cumberbatch.
The 21 films in competition include offers from Australia, China, France, Israel, Poland, South Africa and Venezuela. They face a jury headed by Mexican director Alfonso Cuaron, and nine jurors including actresses Diane Kruger and Elizabeth Banks, Turkish director Nuri Bilge Ceylan and British director Lynne Ramsay.
The line-up includes "great films by auteurs, the return of great masters and many directors showing in the competition for the first time," Barbera told a press conference on Wednesday, promising "surprising, particularly innovative" flicks this year.
Sex, rock stars and revenge
Competing for the US, director Cary Fukunaga will show child soldier drama 'Beasts of No Nation', while Drake Doremus presents 'Equals', a futuristic love story said to echo George Orwell's novel '1984', in which emotions have been eradicated.
All eyes will also be on stop-motion animated film "Anomalisa" written by Charlie Kaufman - the Oscar winning screenwriter behind 'Being John Malkovich' and 'Eternal Sunshine of the Spotless Mind' - about a man who is crippled by a mundane life.
There is already a buzz about Britain's Eddie Redmayne, who stunned critics with his portrayal of Stephen Hawking in 'The Theory of Everything', and his performance as one of the first people to have sex reassignment surgery in Tom Hooper's 'The Danish Girl'.
Michael Keaton will be back on the Venetian Lido island after his 'Birdman' triumph with Tom McCarthy's 'Spotlight', playing out of competition, based on the true story of the Boston Globe's investigative coverage of the Catholic child abuse scandal.
Italy is also a strong contender for the coveted Lion this year with a new horror flick from Marco Bellocchio - whose "Dormant Beauty" competed in 2001 - called 'Blood of My Blood', about a man who is seduced by a nun and her grisly fate.
French actress Juliette Binoche will star in 'The Wait' by first-timer Piero Messina, who has studied under Oscar-winner Paolo Sorrentino and appears to have picked up many of his visual tricks in his Sicily-set story about the relationship between two women.
Italian director Luca Guadagnino is also in the running with US thriller 'A Bigger Splash', starring Tilda Swinton and Ralph Fiennes, about a famous rock star and a filmmaker whose lives are turned upside down by the arrival of an old friend and his daughter.
Other high-calibre international auteurs this year include Amos Gitai, Alexander Sokurov, Pablo Trapero and Atom Egoyan.
Egoyan will be presenting 'Remember', a revenge drama starring Christopher Plummer, in which he plays a man who hunts down a Nazi guard who murdered his family 70 years earlier and is now living in the United States under an assumed identity.