A statement issued late on Wednesday said that President Faure Gnassingbe had accepted Prime Minister Gilbert Fossoun Houngbo's resignation but the former United Nations diplomat would temporarily continue to run daily business.
No official reason was given for the resignation and close aides to Houngbo did not comment.
Houngbo was virtually unknown on the Togolese political scene when he was named prime minister in 2008. He was kept in the post following Gnassingbe's re-election in May 2010.
Togo is due to hold parliamentary elections in October. In recent weeks, there have been a number of protests in the former French colony ahead of the poll as opposition groups seek to reverse changes to voting rules.