"It's truly an overwhelming privilege to be asked to host the Oscars," MacFarlane said in a statement.
"My thoughts upon hearing the news were, one, I will do my utmost to live up to the high standards set forth by my predecessors; and two, I hope they don't find out I hosted the Charlie Sheen Roast."
The annual Academy Awards is Hollywood's big night to pay tribute to the film industry and honor the year's best films, actors and actresses, and the hosting helm is a coveted spot, held by the likes of Frank Sinatra, Johnny Carson, Whoopi Goldberg and Steve Martin.
Comedian MacFarlane, 38, has risen to fame as the creator of Fox's hit edgy comedy animated series "Family Guy," which follows the outrageous antics of Peter Griffin and his dysfunctional family.
He also made his directorial debut on the big screen this year with "Ted," an R-rated comedy film starring Mark Wahlberg and Mila Kunis, about a pot-smoking, foul-mouthed teddy bear.
MacFarlane, who voices the characters of Peter, Brian and Stewie on "Family Guy," has often embraced song and dance numbers on the animated show and has hosted "Rat Pack"-themed nights at his home in Los Angeles where he performs.
Oscars telecast producers Craig Zadan and Neil Meron said they picked MacFarlane because "his performing skills blend perfectly with our ideas for making the show entertaining and fresh," calling him the "consummate host."
The comedian follows in the footsteps of this year's host Billy Crystal, a veteran host of the Oscars, and 2011's rookie hosts, Anne Hathaway and James Franco.
The 85th Academy Awards are scheduled for February 24, 2013, in Los Angeles.