The decision was made after the Mariners were defeated by Doncaster Rovers.
Hurst, a Rotherham United stalwart in his playing days, took charge of Grimsby back in December 2020.
He has been axed with the club sat 21st in the League Two table, just four points above rock-bottom Sutton United.
His assistant, Chris Doig, has also departed the club.
Grimsby’s chairman Jason Stockwood said: “It is with sadness and disappointment that we’ve reached this point. Since May 2021, we’ve had a positive relationship with Paul and Chris.
"We’re proud of our achievements under their leadership: our promotion from the National League, the historic FA Cup run, and attaining our highest league position in 17 years.
“However, it’s time to embark on the next phase of the club’s development.
“We’re grateful for their hard work and wish them future success. They are an indelible part of our history and will always be welcome at Blundell Park.”