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First-time Oscar producers Neil Meron and Craig Zadan recruited MacFarlane in a bid to inject a greater sense of the unexpected, and hopefully bigger television ratings, a year after veteran host Billy Crystal performed his ninth stint at the helm of the live broadcast.
And MacFarlane fully embraced his role as provocateur-in-chief.
In an opening monologue and package of song-and-dance numbers obviously calculated to live up to, and even lampoon, his own reputation for pushing the boundaries of taste, MacFarlane put his biting, sardonic brand of humor front and center.
He started off joking that Best Picture front-runner and eventual winner, "Argo," about a real-life clandestine CIA operation to rescue American hostages from Iran, was "so top secret that the film's director is unknown to the Academy."
The barb was a not-so-subtle jab at members of the Academy of Motion Picture Arts and Sciences for failing to nominate Ben Affleck as best director for the critically acclaimed film.
"They know they screwed up," MacFarlane added, as the camera panned to a shot of Affleck, looking somewhat uncomfortable in his seat. "Ben, it's not your fault."
The edgy quotient quickly escalated as MacFarlane described another best-film candidate, "Django Unchained," as the slavery-era "story of a man fighting to get back his woman who has been subjected to unthinkable violence - or as Chris Brown and Rihanna call it, a date movie."
The punch line reference to the physical abuse involved in the relationship between the two R&B singers - Brown pleaded guilty to assaulting Rihanna in 2009 - drew an audible groan from the star-studded Dolby Theatre audience.
"Oh, no, that's what we were afraid he would do," MacFarlane dead-panned.
Lustier groans came later in the evening when MacFarlane, talking about the portrait of the 16th president of the United States in the Oscar-nominated film "Lincoln," quipped that "the actor who really got into Lincoln's head was John Wilkes Booth."
"One-hundred and fifty years (since Lincoln's assassination) and it's still too soon, huh?", MacFarlane laughed, seemingly taken aback at the response.
MacFarlane's performance should not have come as too big a surprise. The comedian, actor and singer made his mark as creator of the animated TV series, "Family Guy," a show known for its ribald satire, much of it aimed at Hollywood conventions.
And MacFarlane, 39, wasted no time in sending up his own risqué persona, in a comedy bit with actor William Shatner, who joined the host on stage via a video screen in the character of Captain Kirk from the sci-fi TV and film series "Star Trek."
In his fictional drop-in visit from the future, Shatner warns MacFarlane he is "destroying the Academy Awards" with jokes that are "tasteless and inappropriate."
But the interlude segued into a song-and-dance number by MacFarlane showcasing his vocal chops to a tune called "We Saw Your Boobs," in which he rhapsodically ticked off the names of various A-list Hollywood actresses who have bared their breasts in films over the years.
Admonished by Shatner to sing songs that celebrate the movies rather than mock them, MacFarlane proceeded to deliver a more respectful rendering of the showbiz standard, "The Way You Look Tonight," joined on stage in elegant dance by actress Charlize Theron ("Snow White and the Huntsman") and actor Channing Tatum ("Magic Mike").
In the way that many cartoons, including MacFarlane's own "Family Guy" series, operate on different levels for kids and their parents, this year's Oscar telecast seemed especially designed to play to more than one TV audience.
Early reviews of MacFarlane's maiden performance were mixed. The Washington Post called it "a fairly middle-of-the-road job as host," while USA Today said it appeared to be an "audition for his own variety show."
The Los Angeles Times was more upbeat, saying he "alternated between making hamburgers out of Hollywood's sacred cows and showing fealty to good old-fashioned showbiz spectacle."
MacFarlane's more provocative turns were offset by some of the more traditional pomp typical of Hollywood's biggest night, including a 50th-anniversary montage salute to James Bond films, capped by veteran singer Shirley Bassey, now 76, reprising her title song from the 1964 film "Goldfinger."
In another highlight of the evening, songstress, actress and director Barbara Streisand, 70, took the stage to perform her signature hit "The Way We Were," from her 1973 film of the same name, in a tribute to the song's Oscar-winning composer, Marvin Hamlisch, who died last year.
In addition to hosting, MacFarlane was a best-song nominee himself this year for writing the lyrics to the song "Everybody Needs a Best Friend" from his R-rated comedy hit film "Ted," about a pot-smoking, foul-mouthed teddy bear.
The award went to "Skyfall," the title song from the latest Bond film, performed at the Oscars by British vocalist Adele.