"Elder Scrolls" was created by Bethesda Studios and received the covered Vector Monkey award, which was the top honor at Saturday's gala at Sony Studios.
The game also helped propel Bethesda to the Studio of the Year award. The suburban Washington studio received four nominations overall.
Spike TV said multiple awards went to "Portal 2," which won five Vector Monkeys, and "Batman: Arkham City," which earned four monkeys.
The Most Anticipated Game award went to "Mass Effect 3."
The event drew plenty of real-life celebrities as well. Zachary Levi, star of NBC's "Chuck," was the host and the rock band Black Keys performed. Also in attendance were Charlie Sheen, LL Cool J, Tony Hawk, Brooklyn Decker and a bevy of other stars.