The 47-year-old was appointed in June 2022 for his second stint with the Seasiders having previously managed them between November 2012 and January 2013.
However, they are without a win in their last 10 Sky Bet Championship matches, with their last league win coming in October 2022 - a 2-1 victory over Coventry.
Appleton's final game in charge was a 2-0 defeat to Watford at the weekend which saw Blackpool sink to second bottom in the table. The club also confirmed that assistant head coach David Kerslake has left Bloomfield Road. A statement on Blackpool's website said: "The club would like to thank Michael and David for their efforts during their time at Bloomfield Road and wish them all the best for the future. "The club hope to be able to announce a new head coach in the coming days."
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