Clooney's political drama is among 23 films - five from Hollywood - vying for the coveted Golden Lion, which will be awarded Sept. 10.
The jury will be headed by American director Darren Aronofsky, a two-time Golden Lion winner whose "Black Swan" was launched to huge Oscar success after opening in Venice last year.
"The Ides of March" tells the story of an ambitious campaign press secretary, played by Ryan Gosling, who gets swept up in a political scandal in the last frantic days of a heavily contested primary race. The film, which also stars Philip Seymour Hoffman and Paul Giamatti as rival campaign managers, is adapted from the play "Farragut North" by Beau Willimon.
Clooney said the movie was ready to begin filming when Barack Obama was elected U.S. president in 2008.
"Suddenly, a cynical film about politics seemed badly timed. Everyone was too optimistic," Clooney wrote in film notes. "It only took about a year before all the optimism evaporated and the timing seemed perfect."
In all, 66 films will make their world premiere at the 68th edition of the world's oldest festival. It is the first time since World War II that all feature films in the festival's three official events - in competition, out of competition and the "Horizons" avant-garde section - are world premieres.
Nearly half of the festival's lineup is high-powered English-language films, a sign of its growing prestige in the eight years that it has been directed by Marco Mueller.
The strong selection also includes Roman Polanski's "Carnage," an adaptation of the Broadway show "God of Carnage," featuring Jodie Foster, Kate Winslet and Christoph Waltz; David Cronenberg's take on psychoanalysis, "A Dangerous Method," featuring Keira Knightley, Viggo Mortensen and Michael Fassbender; and "Shame," a drama by British director Steve McQueen featuring Fassbender and Carey Mulligan.
Other American movies in competition include end-of-the-world film "4:44 Last Day on Earth" by Abel Ferrara; "Dark Horse" starring Mia Farrow and Christopher Walken and directed by Todd Solondz; "Killer Joe," a black comedy by William Friedkin starring Matthew McConaughey in the title role; and the second feature film by Ami Canaan Mann, "Texas Killing Fields," a murder drama featuring Sam Worthington and Jessica Chastain.
One of the most highly-anticipated events at Venice this year is Madonna's second feature film, the U.K. production "W.E." The movie, which premieres out of competition Thursday, intercuts between the romance of a modern woman (Abbie Cornish) and the relationship of American socialite Wallis Simpson and Britain's King Edward VIII, who abdicated the throne for love in the 1930s.
"It is very important because she is a very interesting filmmaker and very personal filmmaker," Mueller said. "She already proved that with her first feature. Even more so in her sophomore film, 'W.E,' you would feel like it is such a celebrated love story, the love story of the century."
Pacino has an out-of-competition biopic, "Wilde Salome," one of seven American movies being show at side events. Featuring Jessica Chastain, "Wilde Salome" is an exploration of Oscar Wilde's work that combines documentary and film, much like Pacino did in his previous "Looking for Richard."
Mueller maintains his strong commitment to Asian film in this year's festival, with one Japanese, one Taiwanese and two Hong Kong films in competition.
Taiwanese director Wei Te-sheng's "Warriors of the Rainbow: Seedig Bale" is stirring hopes that the island's film industry is ready for a comeback after two decades in the doldrums. The four-hour epic about a 1930 aboriginal uprising against Taiwan's Japanese rulers was 10 years in the making and had a $24 million budget, which is huge for a Taiwanese film.
Hong Kong filmmaker Johnnie To's "Life Without Principle" was announced as a surprise movie earlier - and the festival hinted another surprise movie is yet to come.
Mueller has made surprise films a feature of the Venice festival since he took over in 2004. Often their announcement is delayed until after the festival opens, due to political sensitivity or production schedules.