The Detroit rapper also took the award for "Best Hip Hop", an honour which he appeared to find slightly baffling.
Mendes also won the Biggest Fans award earlier in the evening, and is still up for Best Artist - against Ariana Grande, Ed Sheeran, Kendrick Lamar, Miley Cyrus and Taylor Swift.
The star-studded ceremony at the SSE Wembley Arena saw performances from grime star Stormzy, pop group Clean Bandit and former One Direction member Liam Payne.
British R&B singer Rita Ora performed the hosting duties, as well as a mashup of her 2017 hit Your Song, alongside her new single Anywhere.
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.
Hosted by pop singer Rita Ora, the event was also attended by London mayor Sadiq Khan who helped bring the EMAs to the capital as part of his LondonIsOpen campaign.
Mendes performed "There's Nothing Holdin' Me Back", the victor of "Best Song".
Check out footage from Liam's performance below... She later changed into glittery black trousers and a belted black top to perform two of her newest hits: "Sorry Not Sorry" and "Tell Me You Love Me".