Owen Van Natta, whose resignation is effective immediately, will be replaced by Mike Jones and Jason Hirschhorn as co-presidents, News Corp said on Wednesday.
Van Natta could not be reached immediately for comment.
News Corp acquired MySpace in 2005 for $580 million. Since the acquisition, the Internet site has lost ground to rival Facebook, which now ranks as the world's No.1 social network with roughly 400 million active users.
News Corp chief Rupert Murdoch replaced MySpace co-founder Chris DeWolfe with Van Natta last year, betting that the former No. 2 executive at rival Facebook could freshen up the company.
But rekindling MySpace's popularity in the fast-changing Internet world has proven challenging. And analysts have expressed doubt that MySpace will be able to renew its $300-million-a-year search advertising deal with Google Inc on similarly lucrative terms when the deal expires this year.
News Corp said in its quarterly earnings call last week that advertising and search revenue declined at MySpace and that it was taking longer than expected to achieve revenue goals at MySpace.
Owen took on an incredible challenge in working to refocus and revitalize MySpace, and the business has shown very positive signs recently as a result of his dedicated work, said News Corp Digital Media CEO Jon Miller
However, in talking to Owen about his priorities both personally and professionally going forward, we both agreed that it was best for him to step down at this time. I want to thank Owen for all of his efforts.
Jones and Hirschhorn both also joined MySpace in April 2009 with Van Natta.
(Additional reporting by Peter Henderson; editing by Carol Bishopric, Gary Hill)