Shot in black-and white, the movie chronicles a broadcast journalist’s battle against the communist witch-hunt of 1950s America.
It features the real-life conflict between TV news pioneer Edward R Murrow, played by David Strathairn, and Senator Joseph McCarthy.
As well as directing and co-writing the film, which contains newsreel footage of McCarthy himself, former ER star Clooney also stars as Murrow’s producer Fred Friendly.
Robert Downey Jr, Patricia Clarkson and Jeff Daniels also star in the movie, which Clooney has been desperate to make for years.
Oceans Twelve star Clooney’s father was a news anchor for 30 years and Murrow was considered a hero by the family.
Clooney, 44, made his directorial debut in 2002 with Confessions of a Dangerous Mind, an adaptation of the memoirs of game show impresario Chuck Barris, reports Ireland Online.
According to BBC, the former ER star has wanted to make the film for years.
His father was a TV news anchor for 30 years and Mr Murrow was considered a hero by the family.
Robert Downey Jr, Jeff Daniels and Patricia Clarkson also star in the film.
Goodnight and Good Luck is one of 19 movies vying for the prestigious Golden Lion.
Others include The Constant Gardener, starring Ralph Fiennes, the Kate Winslet musical Romance and Cigarettes, and Ang Lee's western Brokeback Mountain.
The festival officially opened on Wednesday with Seven Swords, a martial arts epic set during the 17th Century Ching dynasty.