The role-playing game beat the likes of Modern Warfare 3, Diablo 3 and Mass Effect 3 to the prize.
Skyrim also picked up the 'Best RPG' award and the 'Top Gaming Moment' for its Throat of the World sequence.
Elsewhere, the Digital Spy-sponsored 'Action/Adventure' award was won by Batman: Arkham City, while Battlefield 3 was deemed the 'Best Shooter'.
EA Sports and FIFA were awarded the prize for 'Outstanding Contribution', with the football sim also picking up 'Best Sports'.
Stephen Fry made a surprise appearance to award Uncharted: Golden Abyss with the 'Best Handheld' gong.
The prize was handed out by a robotic version of the television presenter, who was operating the machine from his home.
This year's Golden Joystick Awards have smashed voting records, doubling the number of votes cast for last year's awards.
The Golden Joystick winners in full:
Best Action/Adventure in association with Digital Spy: Batman Arkham City
Best Strategy: Civilisation 5: Gods & Kings
Best Mobile/Tablet: Angry Birds Space
Best Downloadable: Minecraft (360)
Best Fighting: Mortal Kombat Komplete Edition
Best Shooter: Battlefield 3
Best MMO: World of Tanks
Best Handheld Game: Unchartered: Golden Abyss
Top Gaming Moment: The Elder Scrolls 5: Skyrim: Throat of the World
One to Watch: Grand Theft Auto 5
Best DLC: Portal 2: Perpetual Testing Initiative
Best RPG: The Elder Scrolls 5: Skyrim
Best Sport: FIFA 12
Best Racing: Forza 4
Outstanding Contribution: EA Sports & FIFA
Ultimate Game of the Year: The Elder Scrolls 5: Skyrim
Watch a trailer for Skyrim below: