The film, simply titled "Lombardi," is being written by "Forrest Gump" scribe Eric Roth.
"Lombardi" will focus on the years the coaching legend brought the NFL's Green Bay Packs back to prominence in the 1960s. During a nine-year stretch, Lombardi's Packers won five NFL titles.
He died in 1970 after a battle with cancer. He was 57.
"There are few actors who could accurately portray the fire, passion and grit of Lombardi, and we're thrilled to have Robert De Niro on our team," said Charles Coplin, the NFL's vice president of programming.
The film is slated to debut the week before Super Bowl XLVI in February 2012.
De Niro was last seen in the 2009 dramedy "Everybody's Fine," co-starring Drew Barrymore, Kate Beckinsale and Sam Rockwell.
He currently has three films awaiting release – the "Meet the Fockers" sequel "Little Fockers," Robert Rodriguez's action film "Machete" and the crime drama "Stone" with Edward Norton and Milla Jovovich.
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