Following the Oscars, the Family Guy creator hosted 500 people at an after-party at the Lot in West Hollywood.
Accompanied by a 100-piece orchestra, MacFarlane performed a few numbers for guests including "Someday."
While attendees indulged in cocktails named after Family Guy characters, MacFarlane chatted up Charlize Theron, an onlooker tells PEOPLE.
"He spent most of the time talking to Charlize and laughing," the source adds. "Most others just went by to shake hands and make small talk."
Aside from Theron, other guests included Steven Tyler, Joseph Gordon-Levitt, Glee's Matthew Morrison, Darren Criss, Chord Overstreet and Harry Shum Jr., the Vampire Diaries' Nina Dobrev, Twilight's Peter Facinelli and more.
– Jennifer Garcia