Former Leicester and Scotland boss Levein helped St Johnstone avoid relegation last season after taking charge in November.
But the 59-year-old, who also managed Hearts and Dundee United, oversaw four defeats in St Johnstone's five league matches this term, leaving them languishing in 10th place in the 12-team table.
St Johnstone fans chanted "Craig Levein, we want you to go" in the closing stages of last Saturday's 2-0 defeat at Hibernian and they got their wish on Tuesday.
"The board of directors can announce that St Johnstone Football Club has today parted company with manager Craig Levein," a statement said.
"The football club would like to place on record its thanks to Craig for all of his efforts during his time at McDiarmid Park. A further update will follow in due course."
Levein managed Scotland from 2009 to 2012 and won 10 of his 24 matches.