Airing live on MTV, the show was held at Prudential Center in Newark, New Jersey.
Maniscalco's monologue followed a pride-filled performance by Taylor Swift who opened the VMAs in true Swift style, exploding onto the stage backed by drag queens.
She sang songs from her new album You Need To Calm Down and Lover during the colourful, supercharged set to kick off the festivities.
Swift and fellow pop princess Ariana Grande led the nominations, with 10 each. Billie Elish and Lil Nas X had several nods.
In the most-anticipated moment, Miley Cyrus hit the stage with her new hit Slide Away, understood to be about her breakup with Australian actor Liam Hemsworth.
Aired in black and white, an emotional Cyrus sang the heartbreaker in a stripped-back setting featuring only backup singers and a microphone stand.
Her emotional performance was well-received, with many in the crowd giving her a standing ovation, which will no doubt ruffle feathers of the Hemsworth camp who have claimed through sources the breakup was Cyrus' doing.
We were gifted another Disney Channel flashback as the Jonas Brothers, who recently reformed after a lengthy hiatus, belted out their newest songs outside the venue, ushering through crowds of screaming girls.
When presenting the award for Video of the Year, which went to Swift for You Need To Calm Down, John Travolta attempted to hand the statue to RuPaul's Drag Race alum, Jade Jolie, who he obviously thought was Swift.
Try not to cringe to death.
The big honour of the night, the Video Vanguard Award, was presented to Missy Elliott in what the industry deemed a long overdue nod.
Rapper Cardi B presented the award, which garnered a standing ovation from the crowd of A-listers and chants of "Missy" echoing through the venue.
"I never thought that I would be standing up here receiving this award. I promise you it don't go unnoticed the support and love you have shown me over the years," she said.
Elliott pointedly called the award the "Michael Jackson Video Vanguard" during her acceptance speech, following earlier controversy about the late singer's name being attached to the award in the wake of the Leaving Neverland scandal.
She also thanked MJ's sister Janet Jackson for being a true friend during the speech.
Before her speech, the hip-hop veteran and four-time Grammy winner performed a medley of her biggest tracks in a wild set.
Click here for a list of the all the winners.
