The Pirates of the Caribbean star then made a cheeky joke about needing work in what was clearly a pre-recorded segment.
"I just want you guys to know I'm available for birthdays, bar mitzvahs, weddings, wakes ... Any old thing you need," Depp was heard saying.
"And you know what? I needed the work."
Fans of Amber Heard took to Twitter to label the stunt "embarrassing".
Others jumped to defend the actor, declaring they were happy to see him.
Elsewhere, Fergie made her long-awaited comeback to live performing for the first time in four years, opening the show singing one of her biggest hits, Glamorous, where she was joined by Harlow.
The Black Eyed Peas singer wore a sparkling two-set with the words '"First Class" emblazoned across her top and skirt.
Lizzo followed up the opening number with a high-energy showing of her latest hits, About Damn Time and 2 Be Loved.
One of the early winners of the night, who else but Taylor Swift?
The pop powerhouse made a surprise appearance at the awards ceremony, where she accepted the award for Best Longform Video for the 10-minute version of her heartbreak anthem, All Too Well.
"Thank you for this beautiful indication that we did something right," Swift said.
Snoop Dogg couldn't have been any more on-brand with his performance, where he was seen holding a giant joint.
The rapper performed alongside Eminem in a set which kicked off with the two appearing as animated characters before they hit the stage in real-time.
Tonight's Michael Jackson Video Vanguard honouree, Minaj, performed a full career-spanning medley, starting with her show-stealing verse in the 2010 Kanye West single Monster and ending with a performance of her latest single, the US number one Super Freaky Girl.
Earlier, it was all about the red carpet, before celebrities headed inside the Prudential Centre where a star-studded line-up of performers are taking the stage, including Eminem, Snoop Dogg, Blackpink and Eurovision rockers Maneskin.
On the awards front, Harlow is leading the nominations alongside Harry Styles, with eight nods apiece. Billie Eilish, Drake, Dua Lipa, Ed Sheeran, The Weeknd and Taylor Swift trail closely behind with five nominations each.
