The 47-year-old made his managerial debut this season, having served as defensive line coach at the NFC West side since 2007, but has been dropped after his 5-11 record saw them miss the playoffs for the second straight year.
"Jimmy has been a valuable member of the 49ers organisation for the last nine years," Niners CEO Jed York said in a statement. "We all know he is a man of high character, and his contributions on the field and in our community have always been greatly appreciated.
"This entire organisation is proud and grateful to have worked so closely alongside Jimmy. We all wish him and his family great success in the future."
Tomsula, whose promotion to the top job had been something of surprise, ended his tenure on Sunday with a 19-16 victory over the St Louis Rams at the Levi's Stadium.