This further complicates Democratic hopes of maintaining control of the Senate in 2014, as Rockefeller's longevity and popularity meant that the Democrat could reliably hold a seat in deep red West Virginia.
With his exit, the seat could very well easily go to a Republican.
The 75-year-old Rockefeller was one of the most senior in the body and is the chairman of the Commerce Science and Transportation committee.
Rockefeller is holding a press conference at 11 a.m. to discuss his decision. We'll update with more details.
UPDATE: Rockefeller, in a speech announcing his retirement, reflected on his achievements. He mentioned avoidance of a nationwide coal strike and the wooing of Toyota and 21 other Japanese companies to West Virginia.
Rockefeller believes "the peak moment of his career" was threatening to keep the Senate in over Christmas if they didn't pass the 1992 Coal Act, which established lifetime health benefits for coal miners.
He's been "proud to stand with the working men and women of America" throughout his career.