Llorente, who will continue as a director, announced the decision at a board meeting on Friday, reportedly in protest at boardroom changes at the club.
The club also confirmed Jose Antonio Garcia Moreno had resigned as vice-president.
"Today I informed the board of my resignation from the presidency of Valencia. I go with the conscience of a job well done," Llorente, who became president in June 2009, was quoted as telling a press conference.
Valencia lie sixth in the Primera Division table.