Bowyer, 47, took charge of Blackpool in 2016 after the club were relegated to League Two and secured immediate promotion back to League One in his first season in charge.
"It has been a pleasure to manage Blackpool Football Club over the past two years," he said after becoming the first manager in England's top four divisions to depart this season.
His assistant Terry McPhillips will take charge of the club on an interim basis. Blackpool's next match is a league fixture at home against Portsmouth on Saturday.
(Reporting by Simon Jennings in Bengaluru; Editing by Christian Radnedge)
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