Swift won the Video of the Year for "Fortnight," which also featured Post Malone, and thanked her loyal Swifties for bestowing her with the fan-chosen award, which she took home for the third straight year.
"To the fans, I'm always trying to figure out a way to say thank you to you for making my life what it is," Swift, who directed the video, said onstage.
"If you are over 18 please register to vote for something else that is very important," she added.
The 34-year-old international megastar's call follows her endorsement of Kamala Harris in the minutes after the previous evening's presidential debate between the Democratic hopeful and Republican Donald Trump.
"I'm voting for @kamalaharris because she fights for the rights and causes I believe need a warrior to champion them," Swift said in a lengthy Instagram post in throwing her support behind the Democratic nominee.
Also among the night's big winners was Chappell Roan, the "Midwest Princess" whose career has skyrocketed in recent months.
She wore a full suit of armor as she took the stage with a fiery crossbow to channel Joan of Arc in her performance of "Good Luck, Babe!" set in front of a flaming castle.
She dedicated her Best New Artist trophy to "queer and trans people who feel hot, to the gays who dedicate my songs to someone they love or hate."
"And for all the queer kids in the Midwest watching right now I see you," the Missouri native continued. "I understand you, because I'm one of you, and don't ever let anyone tell you that you can't be exactly who you want to be."
Performance over prizes
South Africa's Tyla meanwhile won Best Afrobeats for "Water," a result she called "such a big moment for Africa."
"The global impact that 'Water' had on the world just proved that African music can be pop music too," she said to wild applause. "Like this is just so special but also bittersweet, because I know there's a tendency to group all African artists under Afrobeats."
"African music is so diverse -- it's more than just Afrobeats," Tyla said.
The vast majority of awards were doled out offstage during the evening far better known for its performances and stage antics than its prizes.
Megan Thee Stallion hosted, at one point even recreating Britney Spears's iconic 2001 set when she performed with a live python.
Megan's snake was real too -- but she didn't have the same stamina as Brit.
"Come get this snake -- I don't know this snake, this snake don't know me," she shrieked as a handler took the reptile from her arms.
Eminem opened the evening with a recreation of his famous set from the 2000 edition of the awards when he performed "The Real Slim Shady," packing the stage with a crew of his doppelgangers.
Fashion-wise it was an evening for the vamps, including Swift in Dior, with a yellow plaid bustier top and open skirt complete with caged leather gloves and velvet hot pants.
The Reputation-coded outfit was yet another clue for the Swifties that her re-recording of that album was on its way.
And Sabrina Carpenter arrived in archival Bob Mackie -- the same shimmering push-up strapless gown that Madonna wore to the 1991 Oscars.
She dropped from the ceiling on a swing to perform songs including "Espresso" to wide applause.
Carpenter later won the prize for "Song of the Year" for her caffeinated bop.
Anitta brought her signature high-energy twerks to the stage, while Karol G recreated a Latin bar scene to deliver "Si Antes Te Hubiera Conocido."
Katy Perry was bestowed with the evening's top honor, the Video Vanguard prize, which her husband, the actor Orlando Bloom, presented to her.
Perry also emerged from the air, giving a video-game-meets-Cirque-du-Soleil aerial dancing performance of her greatest hits including "Dark Horse" and "California Gurls."
Earlier in the broadcast, while accepting an award with Post Malone for Best Collaboration, Swift acknowledged that this year's show fell on September 11.
She paid homage to those lost in the 2001 attacks, telling the audience "that is the most important thing about today."
