The post-apocalyptic first-person shooter was developed by Bungie. It was the US studio’s first release after quitting the Halo series.
The title attracted mixed reviews, and its relatively bare-bones plot continues to divide gamers.
The award surprised many in the audience at the London ceremony as it had not won any of the other categories it had been nominated for.
However, Bungie’s skill at crafting alien-slaying gunfights appears to have helped it seize the top prize.
BBC Newsbeat’s Jonathan Blake tweeted the reaction to Destiny’s victory from the ceremony Accepting the award Bungie’s president thanked Destiny’s players.
“It’s always a labour of love that we do because of the passion of the fans,” said Harold Ryan.
“They really are the ones who drive you to put the energy and time into putting the game together.”
Several other biggest-budget nominees – including Assassin’s Creed Unity, Mario Kart 8 and Call Of Duty: Advanced Warfare – walked away without a prize.