Youth team coach Abdoulay Konko will serve as interim manager, the Serie A club said in a statement.
Since being hired on Nov. 7 last year, Shevchenko only won one of his 11 matches in all competitions.
Genoa went without a win in Serie A during his tenure and face a relegation battle as they sit in 19th place with just 12 points.
The Ukrainian was a prolific striker who rose to global fame as a player for AC Milan, Chelsea and Dynamo Kyiv.
He won the UEFA Champions League with Milan in 2003, followed by a Serie A title in 2004. He was awarded the prestigious Ballon D'or the same year.
Shevchenko was appointed as Ukraine's head coach in 2016.
He guided the national side to Euro 2020, where they reached the quarterfinals for the first time in their history, but stepped down after the tournament.
