The Mexican filmmaker, 52, fresh off his best director win at the Golden Globes, is up for the prestigious outstanding directorial achievement in feature film prize he took home last year for "Birdman", reported Contactmusic.
He will face off against four-time nominee Ridley Scott, who has won acclaim for "The Martian", and first-timers George Miller (Mad Max: Fury Road), Tom MCCarthy (Spotlight), and Adam MCKay (The Big Short).
The eventual winner will be given a big Oscars boost as the DGA champ typically goes on to repeat their success at the Academy Awards - as Inarritu did in 2015.
The competitors for the TV and documentary categories will be unveiled soon.
The 68th annual DGA Awards will take place in Los Angeles on February 6, with actress Jane Lynch serving as host.
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