Hooper was presented with the outstanding directorial achievement by his peers for his story of stuttering British monarch King George VI.
The DGA prizegiving is thought to be the best indicator for the Oscars, with all but six recipients going on to pick up the Best Director honour at the Academy Awards since 1948.
Accepting the accolade, Hooper paid tribute to his mother, who sparked his interest in the king.
He told the audience, "She came home and she rang me up and she said, 'I think I found your next movie'. The moral of the story is, listen to your mother."
Hooper beat out competition from The Social Network's David Fincher, Darren Aronofsky (Black Swan), Christopher Nolan (Inception), and David O. Russell (The Fighter).
The King's Speech is nominated for a staggering 12 trophies at the Oscars in February (11), including Best Picture.