The superhero blockbuster won Best Hero (Chadwick Boseman), Best Villain (Michael B Jordan), Best Performance In A Movie (Boseman) and the biggest prize of the night, Best Movie.
Accepting the award, Jordan, who plays Erik Killmonger in the hit film, said: "It's incredible when the stereotype was that people of colour couldn't bring people out to the theatre... so the fact we were able to do this on this scale means the world to us.
"It's not just for people of colour, it's universal, it's for all of us."
Jordan's co-star, Winston Duke, added: "Thank you for investing not just in a beautiful story but investing in a continued conversation in what this industry and what this culture can achieve and what we all can aspire to be."
Elsewhere, Netflix's sci-fi drama Stranger Things won the awards for Most Frightened Performance (Noah Schnapp), Best TV Show and Best Performance In A Show (Millie Bobby Brown).
Love, Simon stars Nick Robinson and Keiynan Lonsdale won the Best Kiss award, meaning the prize went to a same-sex couple for the second year in a row.
Cast members from Netflix teen drama 13 Reasons Why presented the award, which was awarded to Ashton Sanders and Jharrel Jerome in Moonlight in 2017.
Accepting the award, 26-year-old Australian actor Lonsdale said: "You can live your dream and wear dresses, you can live your dreams and kiss the one you love, no matter what gender they are."
While accepting the Best Hero award, Boseman, who played the Black Panther, handed over his prize to a fast food customer who saved lives when he fought off a gunman who opened fire in a restaurant.
During his acceptance speech, the 40-year-old called James Shaw Jr on to the stage.
Shaw Jr disarmed an attacker armed with an assault rifle at a Waffle House in Antioch, Tennessee, in April.
Four people were killed in the attack and suspected gunman Travis Reinking was later arrested away from the scene.
Handing over the award on stage in Los Angeles, Boseman told Shaw Jr: "This is going to live at your house."
He later tweeted: "During the show, I was honored to meet @JamesShawJr9. He saved countless lives by tackling a gunman who opened fire on people in Antioch, Tennessee in April. He's a true hero that walks among us."
Also victorious on the night was Keeping Up With The Kardashians, which won Best Reality Series.
Lena Waithe was honoured with the Trailblazer Award and Chris Pratt was given the Generation Award.
Additional reporting by PA.