The pop stars, who have yet to officially confirm they are in a relationship but have been pictured kissing anywhere and everywhere, will take to the stage in New Jersey on Monday 26 August to perform the song, which topped the charts in the UK after it was released in June.
MTV announced the news on Twitter.
Both artists are up for multiple awards at the VMAs, one of the biggest nights in music.
Cuban-American pop star Cabello, 22, earned five nominations, including song of the summer for Senorita, while Canadian singer Mendes, 21, is up for six gongs, including artist of the year.
Cabello and Mendes were first romantically linked following the release of the intense Senorita music video in late June; around the same time, it emerged Cabello had split with her boyfriend, the British dating coach Matthew Hussey.
The alleged couple are yet to officially confirm their romance, but on Mendes’ birthday in August Cabello shared a picture of the pair together on Instagram, along with the caption: ‘I love you’.
Ahead of the VMAs, Ariana Grande and Taylor Swift lead the way in nominations with 12 each.
The coveted video of the year prize is between Grande for Thank U, Next, Swift for You Need To Calm Down, 21 Savage for A Lot, the Jonas Brothers for Sucker and Lil Nas X for Old Town Road (Remix).
The MTV VMAs will take place in the Prudential Centre in Newark, New Jersey, on Monday.