The 39-year-old creator of edgy animated sitcoms 'Family Guy' and 'American Dad', had been billed as the saviour of the show after a series of below par performances by hosts in recent years.
However, he faced a backlash after his performance, with perhaps the most controversial joke being that only one actor had really got "into Lincoln's head" - John Wilkes Booth, the man who assassinated the US president.
Responding to the boos from the audience, the host said, "150 years and it's still too soon."
MacFarlane also sang a song in which he listed a string of actresses in the audience who had appeared topless in films, The Telegraph reported.
In a pot shot at Daniel Day-Lewis, the MacFarlane said, "If you bumped into (black actor) Don Cheadle on the studio lot, did you try to free him How deep does your method go"
He also suggested that the film 'Django Unchained', which features many racial epithets, had been based on Mel Gibson's voicemails - and described the violent movie as singers Chris Brown and Rihanna's idea of a "date movie". Brown famously assaulted his girlfriend Rihanna in 2009.
In one segment he used the animated teddy bear from his hit film 'Ted' to make a joke about Jews controlling Hollywood. The bear, voiced by MacFarlane, said, "I was born Theodore Shapiro and I would like to donate to Israel and continue to work in Hollywood forever."
The Anti-Defamtion League, a Jewish media monitoring group, said it was "offensive and not remotely funny. It only reinforces stereotypes which legitimise anti-Semitism."
Time TV critic James Poniewozik called MacFarlane "American Dud" and said the performance "had a nasty streak, particularly concerning women."