Drake, a Canadian rap artist, won 13 awards, including top artist, top male artist, top Billboard 100 album, top Billboard 200 artist and top Hot 100 artist.
He was nominated for 22 awards, just behind the Chainsmokers, who led with 23 nominations.
Accepting the night's biggest award, top artist, Drake brought up a huge entourage that included Lil Wayne, Nicki Minaj and his father, decked out in a purple suit. "I got my whole family up here," he declared.
The show was kicked off by Minaj, who delivered a rousing nine-minute medley of her latest singles. Minaj, who recently broke Aretha Franklin’s record for female artist with the most Billboard Hot 100 hits, was joined by Lil Wayne, David Guetta and Jason Derulo as she performed a medley of “No Frauds,” “Light My Body Up,” Swalla,” and “Regret In Your Tears.”
Hosting the show for a second year in a row, Ludacris was joined by co-host Vanessa Hudgens, who impressed with both her rapping skills and her vocal chops.
But the night's most memorable performances came from the music veterans, including Celine Dion, who gave a showstopping performance of "My Heart Will Go On," for the 20th anniversary of the movie "Titanic." Introduced by Lea Michele, Dion appeared under a beaded crystal chandelier, in a stunning white gown with voluminous sleeves. As she sang, clips from the movie played. The performance earned Dion, 49, a standing ovation.
The night's other big moment belonged to Cher, who received Billboard's Icon Award. The day after her 71st birthday, the singer took the stage to perform two of her biggest hits, "Believe" and "If I Could Turn Back Time."
Accepting the award from Gwen Stefani, Cher said, "I’ve wanted to do what I do since I was 4 years old ... and I've been doing it for 53 years -- and I can do a five-minute plank."
Among the folks she thanked was her mom, who she said once told her that she wouldn't be the smartest or prettiest but she would be "the most special."
Bad Boy Records mogul Sean "Diddy" Combs made a special appearance to honor what would have been the 45th birthday of Notorious B.I.G. Diddy introduced Biggie's son, Christopher Wallace, and unveiled an exclusive look at the trailer for his new Apple Music documentary, "Can’t Stop Won’t Stop: A Bad Boy Story."
Other big performances included Drake, who rapped his latest single, "Gyalchester," in the middle of Las Vegas famous Bellagio fountains, surrounded by fireworks and the water display.
Earlier, Lorde got the crowd going with her wild dance moves during a karaoke-inspired performance of her song "Green Light." The Chainsmokers gave an electric performance of their latest hit, "Young." And breakthrough artist Julia Michaels gave an emotional performance of her hit "Issues."
Miley Cyrus, who was introduced by her father, Billy Ray Cyrus, and little sister Noah, surprised with her new country-influenced single "Malibu." She teared up she delivered the song's final lines about a "dream come true" and a "brand new start."
Country music was also represented by Sam Hunt, who performed his hit "Body Like a Back Road" and Florida Georgia Line, which joined John Legend for a mashup of its songs "Surefire" and "H.O.L.Y."
After performing its new song, "Believer," Imagine Dragons delivered touching remarks in memory of Chris Cornell, the frontman of Soundgarden and Audioslave, who died at age 52 last week.
The broadcast also featured performances via satellite by Ed Sheeran and Bruno Mars, who are both on tour.