His departure marks the end of a four-year period at the helm of the Grimsby-based club.
Smith's tenure at the Owls saw a period of success, winning back-to-back Lincolnshire Senior Cups in 2018/19 & 2019/20.
The club have stated that Matt Bloomer, Jon Davy and Matty Powell will assume responsibility of the squad ahead of their next fixture against Grantham Town on Tuesday.
Cleethorpes are now accepting applications for the role of first-team manager.
If you are interested, please email your CV to David Simpson at secretary@cleethorpestownfc.co.uk.
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