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The 37-year-old actor beat out tough competition for the coveted award, including Bradley Cooper for "A Star is Born," Willem Dafoe for "At Eternity's Gate", John David Washington for "BlacKkKlansman" and Lucas Hedges for "Boy Erased".
Malek has been nominated for a Golden Globe twice before -- earning a nomination for best actor in a television series in 2016 and 2017 for his performance in "Mr. Robot."
The USA television series is where Malek first rose to prominence, before landing the lead role in the 2018 Queen biopic.
Malek's win, along with the film's win of Best Motion Picture Drama, were two of the most tweeted-about moments of the night, with viewers across the U.S. itching to learn more about the eccentric actor. Here's everything you need to know.
Malek dedicated his big win to the late Freddie Mercury
During Malek's acceptance speech, he praised the late icon for his impact.
“Thank you to Freddie Mercury for giving me the joy of a lifetime," he said. "I love you, you beautiful man. This is for and because of you, gorgeous.”
Malek also said that through playing the character, he was able to draw personal connections with Mercury.
“I tried to find the humanity in him,” he said during a press room speech after the film's win.
“I related it to him being an immigrant struggling to discover his identity," he continued. "I tried to take everything he was struggling with, his complication, his chaos, his turmoil and this beauty inside of him. He lifted me up to be everything I could be in this film.”
Queen was on board with Malek playing their band's leading man
The actor earned the approval -- and praise -- of two of the band's members, lead guitarist Brian May and lead drummer Roger Taylor.
May said they wouldn't have been on board with the film if it didn't include the proper cast.
"It's probably fair to say we were reluctant actually to approach [the] format," May said in a press room speech about adapting their band's story into a film.
"We had this feeling that if we didn't do it, and we didn't do it with the right people, then it would get done wrong by somebody and it wouldn't do Freddie justice," he continued.
He added that if he and Taylor hadn't found the proper cast, "then we wouldn't be standing here."
During Malek's acceptance speech, he praised Queen for, "ensuring that authenticity and inclusivity exists in the music and in the world and in all of us."
Malek sidestepped addressing the film's former director during the Globes
"Bohemian Rhapsody" was surrounded by controversy due to the movie's original director, Bryan Singer, being fired halfway through production in December 2017.
He was replaced with director Dexter Fletcher. The movie studio, 20th Century Fox reportedly said his firing was due to "unexplained absences from the set," according to The Hollywood Reporter. Rumors also surfaced that his firing was due to disagreements with Malek.
However, Singer refuted the claims at the time. "Any discussion about fights between myself and Rami Malek are simply an exaggeration of a few creative differences that were quickly resolved. This is normal on a film set. And I think the work speaks for itself," he told THR.
The same month, sexual assault allegations against Singer surfaced. He was sued for allegedly sexually assaulting a 17-year-old boy over a decade ago.
"Bryan categorically denies these allegations and will vehemently defend this lawsuit to the very end," a representative for Singer told ABC News at the time.
The cast and production heads didn't want the night to be about Singer. When asked about the film's former director, who received credit for directing the film, producer Graham King declined to comment.
"It’s not something I really wish to talk about tonight,” King said.
After another follow-up question regarding Singer's name omitted from all acceptance speeches for the film, Malek spoke up.
“I will take this one,” he said. “There’s only one thing we needed to do, and that was to celebrate Freddie Mercury in this film. Nothing was going to compromise us giving him the love, celebration, adulation he deserves.”
“Every single person that worked on this film collaborated and did it out of the passion of making this story," King added.
Despite the snub, Singer appeared to be celebrating the film's win. He shared a snap on Instagram of himself directing the film.
"What an honor. Thank you #HollywoodForeignPress," he captioned the shot.
Malek embraces political activism
Along with throwing his passion into acting, Malek also encourages his fans to do their civic duty. On the day of the midterm elections in November, he tweeted about voting rights.
We have the power to effect change. Exercise your precious right to #VoteToday!— Rami Malek (@ItsRamiMalek) November 6, 2018
He also voiced his support for Dr. Christine Blasey Ford, the woman who accused now-Supreme Court Justice Brett Kavanaugh of sexual assault.
Thank you for your tremendous strength and bravery, Dr Christine Blasey Ford. pic.twitter.com/ZQvtLVyDPH— Rami Malek (@ItsRamiMalek) September 27, 2018
The actor isn't afraid to jump in on a viral joke
Malek's interaction with a fan turned viral when he was featured in a video refusing a video and offering a photo with the young woman instead.
THIS IS PROBABLY THE MOST EMBARRASSING THING TO EVER HAPPEN TO ME pic.twitter.com/qIesyA3eWQ— xan ?? (@enemyfiIm) October 30, 2018
The moment gained so much online attention that he addressed it. "I finally brought myself to watch it,” he told Vanity Fair. “I thought, ‘Oh, that’s not that bad. I don’t find myself offensive.’”
He later posted a picture with Ellen DeGeneres, captioning the shot, "Always down for a photo."