The pop star is seen in sultry photos taken by photographer Mario Testino for the magazine. In one cover, she sits alone donning a Balmain bodysuit; in two others, she models from atop a man's lap.
"When looking for cover worthy subjects for our 100th issue, we had to ask ourselves, Who do pop stars and musicians -- who have become an integral part of what V represents -- look up to and admire?" said editor-in-chief Stephen Gan in a statement ahead of the milestone issue.
"There was only one answer: Britney!" he added. "She has entered icon status, and who in our world did not grow up listening to her music?"
Spears is currently finishing up her ninth studio album, the magazine reported.
Most recently, the singer -- who got her start in 1999 -- released unofficial video clips for her song "Breathe On Me" on Instagrm.
In the mini music videos for the 2003 tune, the 34-year-old celebrity dances in a bikini.
"Girls just wanna have fun," she wrote in the caption of the first post. "Never released a video for this song...so decided to do a little tease on Instagram instead...enjoy!!"