[2] He made his professional debut with the Arizona League Athletics, playing one game with them, before being promoted to the Vermont Lake Monsters.

He started 2017 with the Stockton Ports and was promoted to the Midland RockHounds in June;[4][5] he batted a combined .250 with 13 home runs and 48 RBIs in 98 games between the two teams.

[12] On December 12, 2022, the Athletics traded Murphy to the Atlanta Braves in a three-team trade, in which the Athletics acquired pitchers Kyle Muller and Freddy Tarnok, along with catcher Manny Piña and minor league pitcher Royber Salinas from the Braves and utility player Esteury Ruiz from the Milwaukee Brewers.

[13][14] Murphy and the Braves signed a six-year contract extension worth $73 million and a club option for the 2029 season.

On March 30, 2024, during the first game of the 2024 season, Murphy suffered a left oblique strain after swinging at a pitch and was subsequently placed on the 10-day injured list.