The three are the first performers announced for the Aug. 28 ceremony in Los Angeles. The announcement was made Thursday.
Brown's once tarnished star is shining bright this year, and MTV has taken note. Amy Doyle, MTV's executive vice president of music and talent, says the network chose Brown because he's "having a moment with multiple hits" and had one of the more memorable performances in the show's history in 2007.
Doyle predicted that Adele will give a chilling and emotional performance. The British singer is nominated for seven VMAs and has the year's best-selling album so far with "21."
Lil Wayne's performance is in conjunction with the release of his much anticipated "Tha Carter IV."
The Associated Press contributed to this report.