Oh, 47, is the first Asian actress to host the awards show, taking place at the Beverly Hilton Hotel in Los Angeles. Hollywood has been buzzing ever since it was announced in December that she and the "Brooklyn Nine-Nine" funnyman Andy Samberg would be co-hosts.
"We are the only two people left in Hollywood not in trouble for saying something offensive," Oh joked about why she and Samberg were picked for the job.
Samberg added, "You fools are all about to get roasted." But then they took turns complimenting their fellow celebs.
Samberg joked about Spike Lee: "Lifetime can't wait to see what you do next!"
Oh took on Bradley Cooper, simply saying, "You are hot."
"Damn, this is live on TV -- no take backs," Samberg teased.
The duo said some sarcastic lines about stars like Michael B. Jordan and Amy Adams. They also spoke about "Black Panther" and "A Star Is Born."
"'Crazy Rich Asians' made over $200 million at the box office, said Asians moms everywhere ... " Oh said as she stared at the crowd.
"Cut to my mom right now!" she added.
But the two closed the monologue in a serious note, alluding to why Oh said "yes" to hosting this year.
"I wanted to be here and look out onto this audience and witness this moment of change," she said passionately. "It may change next year ... but right now, this moment is real. Trust me, it is real, because I see you, all these faces of change."
Later in the night, Oh was the center of attention yet again for winning the Globe for Best Performance by an Actress in a TV Series, Drama.
She was over the moon, screaming "Oh my God," before adding, "I’m so grateful to my family."
"Two people here tonight, I'm so grateful they are here with me, like to thank my mother and father," she said.
Before the show, Oh and Samberg interviewed each other in The Hollywood Reporter and shared similar sentiments about 2018 being a year of change and growth in Hollywood.
Oh pointed out that all of 2018 was historic for Hollywood with a surge of minorities being cast in leading roles.
"How many gazillions of people have seen 'Black Panther' and 'Crazy Rich Asians?' That changes things. Just speaking for my own community, people cried a lot in ['Crazy Rich Asians'], and it's not only because it's a great story and a classic romantic comedy," Oh told THR.
Samberg said this year feels different "in a really good way."
"Change is really, really slow. Time will tell. But if the writers and the helmers are interested in moving the cultural story along, the audience will come with you," Oh added.
Check back throughout the night for a list of winners, the best speeches and much more!