Patrick Dempsey, Robert Pattinson and Chelsea Handler took the stage to honour Witherspoon with the prize. Each individual's address was heartfelt, but Pattinson's was the most shocking.
Pattinson opened his speech by stating that he made his first movie with the Legally Blonde actress, playing Witherspoon's son.
The Twilight star joked about how she reportedly had him "cut" from the film before talking about his second movie with Witherspoon, Water for Elephants.
"I didn't cut you out," said Pattinson. "But I did f**k you."
He continued: "It's not always a bad thing to have sexual chemistry with your mother."
On accepting the accolade, Witherspoon admitted that she was anxious about accepting the award since Sandra Bullock had received it the year before.
"I was really nervous when they told me I was gonna get this award," she said.
Witherspoon went on to thank the people that she has worked with over the years before singling out the women of the world.
"I've gotten to work with incredible people," she added. "I just wanna say to all the girls out there that… it's possible to make it in Hollywood without a reality show. Thank to everybody at MTV… and all my fans."
Previous recipients of the 'Generation Award' include Sandra Bullock, Ben Stiller, Adam Sandler and Tom Cruise.
More from the MTV Movie Awards:
> MTV Movie Awards open with 'Hangover' spoof
> Jim Carrey dons green screen suit for MTV Awards
> Robert Pattinson kisses Taylor Lautner at MTV Awards
> MTV Movie Awards 2011: The winners
Watch Reese Witherspoon receive the 'Generation Award' below (US readers only - contains strong language):