"Holding Me Back" had already won the EMA for best song earlier in the evening, with Mendes thanking his "best friends, Teddy [Geiger], Scott [Harris] & Geoff [Warburton], for writing this song with me".
Performers ranged across genres and generations, and included singer-songwriter Kesha, electronic act Clean Bandit, rapper French Montana, rockers The Killers and former One Direction heartthrob Liam Payne.
Mendes, 19, who launched his career by posting song covers to the internet before getting signed to a record label, also scooped the "biggest fans" award.
Cuban-American singer Camila Cabello was honoured with the best pop prize, while Coldplay snatched the best rock award.
Luckily, the rest of his night was a lot more successful, as he gave a storming performance and picked up the award for Best UK and Ireland Act.
British singer-songwriter Dua Lipa was named best new artist.
Irish band U2 collected MTV's Global Icon gong, previously awarded to Queen, Whitney Houston and Eminem.
Rita Ora took comfort to the next level on the MTV European Music Awards red carpet. The "Suicide Squad" star looked less than impressed when MC Grindah joked it was nice to meet the 67-year-old TV presenter, before Rita Ora - who hosted the ceremony - corrected him.
The previous Video Music Awards saw hip hop artist Kanye West leap on stage to interrupt an acceptance speech by Swift and argue that Beyonce was better.