Kathryn Bigelow won the best director honor for helming the Iraq war drama. She is the first female filmmaker to take home the statuette in that category. She also beat out her ex-husband, "Avatar" director James Cameron, for the best director title.
"There's no other way to describe it; this is the moment of a lifetime," Bigelow said as she took the stage to collect her director trophy.
Earlier in the evening, "Locker" won the prizes for best original screenplay, film editing, sound editing and sound mixing.
"Avatar," the highest grossing film ever, was also in the running for best picture, but lost out to "Locker." It did, however, win the awards for cinematography, visual effects and art direction.
Sandra Bullock won the Oscar for best actress for "The Blind Side."
"Did I really earn this or did I just wear y'all down?" Bullock asked the crowd. "I would like to thank the Academy for allowing me in the last month to have the most incredible ride with rooms full of artists that I see tonight and worked with before, and I hope to work with in the future, who inspire me and blazed trails for us.
"Four of them I've fallen deeply in love with. I share this night and this award with," she said, referring to her fellow nominees Gabourey Sidibe, Helen Mirren, Carey Mulligan and Meryl Streep.
Jeff Bridges, who was previously nominated four times for an Oscar, enjoyed his first win for his lead role in "Crazy Heart."
"Mom and Dad, yeah, look! Whoo!" Bridges said as he picked up his statuette. "Thank you, Mom and Dad, for turning me on to such a groovy profession. Oh, my dad and my mom (the late actors Lloyd and Dorothy Bridges,) they loved show biz so much. I remember my mom, getting all of us kids to entertain at her parties. You know, my dad sitting me on his bed and teaching me all of the basics of acting for a role in 'Sea Hunt.' They loved show biz so much and I feel an extension of them. You know, this, this is honoring them as much as it is me."