The Oscar winning Bourne Identity hero, 39, was the butt of many a joke during the comedy evening, by movie greats such as George Clooney, Clint Eastwood and Robin Williams.
He withstood a barrage of jibes, although the glitzy annual event also featured a serious message of thanks for Damon's contribution to the film industry and his humanitarian work.
Double act: Matt Damon, left, was honoured last night by the world of film when he was handed a American Cinematheque Award by his best friend Ben Affleck
Childhood friends: Damon and Affleck grew up together, dreaming of making it big in Hollywood
At the end of the night, Damon's own entertaining acceptance speech was cut short when he was jokingly shoved off stage by an actor with whom he had made a spoof movie trailer with for the show.
'I think everyone who works in this industry feels lucky to do what they do,' said Damon.
'This is quite a night for me that they are giving me this honour. It is all about supporting the work that they do.'
Damon, a father-of-two whose wife Luciana looked on proudly, joked about his much talked about 'bromance' with childhood buddy Affleck.
Standing ovation: The Good Will Hunting star goes up to collect his gong
Speaking to audience member Robin Williams, who he starred alongside in the 1997 film Good Will Hunting, he added: 'You'll always to be like a teacher to me - a very hairy and emotionally unstable teacher - but a teacher none the less.'
Host Jimmy Kimmel had kicked off proceedings with a series of mock insults directed at Damon.
'This is ridiculous giving salute to someone under 40,' he said. 'Next year lets give it to Vanessa Hudgens.
'I don't have much so say about Matt Damon, just like he didn't have much to say in Oceans 11, 12 and 13.'
Comedy: Damon's Ocean trilogy co-star George Clooney did a recorded message where he pretended to be in the midst of prostate surgery
'You're telling me Matt Damon is better than Clint Eastwood?' said Kimmel.
'Even in the movies with the monkey he was better than Matt Damon!'
Invictus star Eastwood also took to the stage to weigh in with his own entertaining words.
'Let me tell you something, Matt Damon is one of the finest, most versatile young actors working out there today.
'The reason I know that when he came to my office to talk about doing Invictus, he said 'Clint, I'm one of the finest, most versatile young actors out there today'.
Shiny in gold: Charlize Theron joked about the film they made together that bombed at the box office, The Legend of Bagger Vance
Prompting a roar of laughter from the audience, he added: I told him I thought he was too short.'
Damon's Ocean trilogy co-star George Clooney's recorded message sparked a fit of giggles from the audience.
Wearing a hospital gown, the movie hunk claimed to be in the midst of elective prostate surgery and jokingly winced his way through his message.
'Tonight completes you Matt,' he said, through a series of mock painful facial expressions.
Salute: Damon described Robin Williams, who he starred alongside in Good Will Hunting, as like a teacher to him
'Tonight, all of that ends. Tonight you have an American Cinematheque award (laughs). There's nothing left, nowhere else to go
'I have one of those awards Matt and look at me, I'm happy, I'm complete, the world is my oyster.'
Jerking his groin away from a supposed medic, he yelped: 'Don't touch those!' before congratulating his buddy.
A glamorous Charlize Theron strutted on stage in a gold mini dress, and joked about the box office bomb The Legend of Bagger Vance that she and Damon starred in.
High praise: Clint Eastwood described Damon as one of 'the finest, most versatile young actors working out there today'
'Of course, I got mine in a real category and Matt got him for just typing up Affleck's thoughts.'
Theron drew a round of laughs, referring to the Oscar Damon won with Affleck for writing hit Good Will Hunting.
'Joking aside, I'm actually here to present the serious part of tonight's show, Matt has deeply invested himself in non-profit work making it a personal priority.
'It's really easy to praise Matt as a philanthropist. His involvement in charities has contributed to raising millions of dollars.
'Matt's humanitarian achievements are nothing short of inspirational and I think it's because he truly believes the world can be a better place and it's our responsibility to make it so.'
During Bill Clinton's touching tribute, he said: 'I hope Matt's selfless work will inspire all of us to do more and give more with that same compassion, dedication and perseverance that Matt demonstrates every day.
Evening of laughs: Jennifer Garner is amused by something as she sits next to husband Affleck
Stunning brunette Jennifer Garner made fun of her husband Ben Affleck's close friendship with Damon while up on stage.
'Ben is half of one of the greatest love stories every told,' she said.
'Not with me. The actual prototype for the great Hollywood romance - Matt-and-Ben-Ben-and-Matt.
'I've known Matt-and-Ben-Ben-and-Matt as an entity for a while now, we've all been married to each other for five years and I can tell you that what you hear about their friendship, it's true.
'They grew up together, they did high school drama together, they won an Oscar together.'
'Bro-mance': Damon described Affleck as his 'hetero-lifemate'
'I kind of started out the same time with the guy, so this is a special night for me too,' he said.
'Seriously though, in Good Will Hunting I was gonna play the main guy, Matt's part.
'But it felt like it was so on the nose to have me play a genius.
'Who could have imagined Matt would be here tonight? No one.
'Not his parents. Always seemed like they liked me a little more. I don't know, maybe it's just me.
'In all seriousness, Matt is a great guy, my best friend
'It's an honour to present the American Cinematheque Award to my friend Matt Damon.'