The original roster included Sebastian "Zebbosai" Olsson, who would play in the inaugural season of the Overwatch League as the main support player for the Mayhem.

[7][8] The following week, on January 19, they notched their first-ever victory after defeating the Shanghai Dragons 4–0; this would be their only win during Stage 1 of the season.

[9][10] On May 2, head coach Vytis "Mineral" Lasaitis temporarily stepped down from his position, citing that he had been experiencing "various health issues" and burnout since stage two.

Assistant coach Choi "r2der" Hyun-jin and analyst Albert Yeh lead the team in his absence until his return at the beginning of Stage 4.

Florida hired Oh "Unread" Nam-hun amidst a one-win Stage 3 as the team's new head coach.

[14] The Mayhem found success in Stage 4, when the league implemented a 2-2-2 role lock, as they were able to win four of their final five matches.

[16] The Mayhem opened the season going 7–4 heading into the May Melee tournament, where they reached the finals before being defeated by the San Francisco Shock.

[22] After defeating the Toronto Defiant and the Washington Justice in the regional knockouts, the Mayhem advanced to the interregional tournament bracket.

[26][27] Florida Mayhem's 2022 season started on May 5, 2022 with a game against the Atlanta Reign in the Kickoff Clash qualifiers, which they lost 3-1.

Florida Mayhem then played in the Midseason Madness Qualifiers, winning two out of the six of the matches, entering them into the main brackets.

A 0-3 loss to the Seoul Dynasty, a 3-1 win against the Atlanta Reign, and the Hangzhou Spark eliminated Florida Mayhem in Lower Bracket Round 2 to end their 2022 season.