Blizzard's recently-released Diablo III was the first PC-only title to top the US retail game charts since July 2010, according to the NPD Group's May sales data.
StarCraft II, also a Blizzard title, was the last PC title to have the honour.
"PC Games sales realised a year over year increase of 230%," said the NPD Group's video game industry analyst, Anita Frazier.
"Diablo III is the top selling title for May, the first time since July 2010 that a PC-only game accomplished this feat. Since the game launched day and date through digital distribution as well, full sales of the title are some multiple of what is reflected in the retail sales."
"New launches generated 31% more dollars this May than they did last May, largely due to the success of Diablo III."
The second-best selling game for May was Max Payne 3, a PC-native but not PC-exclusive title.
Frazier said there had been a 27% reduction on new game titles introduced into retail stores, year-on-year, contributing to a general 'softness' in May's game sales.