The Fluorescent Adolescent hitmakers, who headed into the ceremony with eight nominations, picked up the first prize of the night, for Best Live Band, and followed it up with the Best Album accolade for Am and Best British Band.
But it wasn't all about the Arctic Monkeys - their hit Do I Wanna Know? lost out to Disclosure's White Noise in the Best Track category, and Best Music Video went to Eagulls for Nerve Endings.
Lily Allen claimed the title of Best Solo Artist, but appeared a little shocked as she collected the trophy and told the crowd, "This is kind of dumb because David Bowie is in this category, and Jake Bugg, so this goes to you guys, not me! Thank you."
Meanwhile, Blur star and Innovation prize winner Damon Albarn was given the honour of introducing Sir Paul MCCartney as the recipient of the one-off Songwriter's Songwriter award, in celebration of his phenomenal career.
As he took to the podium at the O2 Academy Brixton, the Beatles icon recalled reading the Nme magazine during his youth and confessed to pulling off a prank with his Fab Four bandmates years ago, revealing: "One of the things we used to like to do was plant false stories in the Nme and we actually got one in that George (Harrison) was Billy Fury's cousin, but he wasn't...!"
After a brief technical glitch, Blondie were honoured with the night's final accolade, the Godlike Genius award, and they wrapped up the event by hitting the stage for a hits medley, kicking off the set with their 1979 smash One Way or Another.
Other performances during the night came from the likes of The Horrors, Belle and Sebastian, and Metronomy, who teamed up with female trio Mutya Keisha Siobhan to open the show with Love Letters.
The main list of winners at the 2014 Nme Awards is as follows:
Best British Band - Arctic Monkeys
Best Live Band - Arctic Monkeys
Best Album - Am by Arctic Monkeys
Best Track - White Noise, Disclosure
Best Solo Artist - Lily Allen
Best New Band - Drenge
Best International Band - Haim
Best Music Video - Nerve Endings by Eagulls
Best Music Film - Made of Stone, directed by Shane Meadows
Teenage Cancer Trust Outstanding Contribution to Music - Belle and Sebastian
Philip Hall Radar Award - Fat White Family
Songwriter's Songwriter Award - Sir Paul MCCartney
Godlike Genius - Blondie
Innovation - Damon Albarn
Best Festival - Glastonbury
Best TV Show - Breaking Bad