"Good evening ladies and remaining gentlemen," he said at the top, setting the tone for the evening.
Yes, this is a serious topic, but this is also a night of celebration and joy. Humor also works as a coping mechanism and a tool for healing. Both were clearly happening as Meyers threw hard barbs at the likes of Harvey Weinstein, Kevin Spacey, and Donald Trump.
But don't worry, his former "SNL" "Weekend Update" Amy Poehler was there to keep his white male privilege in check when she called him out for "mansplaining."
Here's how the NBC late-night comedian tackled the biggest issues of the night.
"For the male nominees in the room tonight, this is the first time in three months it won't be terrifying to hear your name read out loud," Meyers joked toward the top of the monologue. "'Did you hear about Willem DeFoe?' 'Oh no.' 'He was nominated.' 'Don't do that! Don't do that.'"
Meyers held back nothing regarding #MeToo and its successor, #TimesUp. Just as it has dominated the news cycle in recent months, it absolutely dominated his monologue, but in such a way that he got genuine laughs from the audience, with only a few groans of discomfort.
"It's 2018, marijuana is finally allowed and sexual harassment finally isn't," he quipped at one point. He even worked it into discussions about the nominees, saying, "This was the year of big little lies and get out, and also the television series 'Big Little Lies' and the movie 'Get Out.'"
Meyers wasn't shy about going for the jugular, either, calling out Harvey Weinstein and Kevin Spacey by name. He probably got the rawest reaction for his joke about Weinstein, but he was prepared with a quick response to that as well.
"I think it's time to address the elephant not in the room," he said. "Harvey Weinstein isn't here tonight because, well, I've heard rumors that he's crazy and difficult to work with. But don't worry, he'll be back in 20 years when he becomes the first person ever booed during the In Memoriam."
When the audience loudly reacted to the joke, Meyers added, "It'll sound like that."
While rattling off some of the events of the year, Meyers noted, "They're gonna do another season of 'House of Cards.' Is Christopher Plummer available for that, too? I hope he can do a southern accent, because Kevin Spacey sure couldn't."
Somehow that joke also elicited an audible response from the audience, leading to Meyers' response: "Oh was that too mean? To Kevin Spacey?"
Later, he upped the ante during a segment from "Late Night" he ported over where he gives the setup to a joke and then a minority gives the punchline, because it's just going to sound better coming from someone who isn't a straight, white male.
Billy Eichner, who is openly gay, got the privilege of wrapping this joke: "'Call Me By Your Name' is nominated for Best Motion Picture. It is a gay coming-of-age film." Eichner added, "Said Kevin Spacey, You lost me at 'of age.'"
When it came time for Poehler to play the game, she was having none of it. "I'll do one, but I don't need your help," she told Meyers. When he tried to reiterate the premise of the bit, Poehler interrupted him, "Oh is that how it works? You're explaining something I already know. Is this the mansplaining part of the evening?"
She was adamant about doing the joke on her own. "I'm a woman in Hollywood. We've all been through a lot," she explained. "I don't need a setup to make a punchline work, okay? You're sadly mistaken."
She then let it rip: "Said the peach in 'Call Me By Your Name,' this scene is the pits."
Meyers even took himself to task for being the host of the show. "They tried to get a woman to host this show, they really did. They said, 'Hey, how would you like like to come and be judged by some of the most powerful people in Hollywood,' and women were like, 'Hhmmm, well where is it?' and they said, 'It's in a hotel--' and long story short, I'm your host tonight."
He tried to soothe the audience by telling them, "If it's any consolation, I'm a man with absolutely no power in Hollywood. I'm not even the most powerful Seth in the room tonight." Cameras then cut to Seth Rogen, who could only nod and agree.
Some of the night's ammunition was saved for the President of the United States, including a clever take at the name of the event's host.
"We're all here tonight courtesy of the Hollywood Foreign Press, a string of three words that could not have been better designed to infuriate our president. Hollywood. Foreign. Press," Meyers mused. "The only name that would make him angrier would be the Hillary Mexico Salad Association."
After introducing Oprah Winfrey as the evening's recipient of the Cecil B. DeMille award, he recalled that in 2011 he gave a speech where he said Trump wasn't qualified to be president. He explained that some have said this may have been a reason Trump ran.
So Meyers took the opportunity to address Winfrey. "If that's true, I just want to say, Oprah you will never be president. You do not have what it takes!" He then looked for Tom Hanks. "You will never be vice president," he told him. "You are too mean and unrelatable." Turning back to the camera with a wry smile, he concluded, "Now, we just wait and see."