Merrill began his professional career in the Padres' minor league system, showing consistent development. He made his MLB debut on March 20, 2024, against the Los Angeles Dodgers in the Seoul Series. In his rookie season, Merrill posted impressive numbers: a .292 batting average, 24 home runs, 90 RBIs, and 16 stolen bases. His performance earned him a selection to the 2024 MLB All-Star Game, a Silver Slugger Award, and a spot on the All-MLB Second Team.

In April 2025, Merrill signed a nine-year, $135 million contract extension with the Padres, which includes a $30 million team option for a 10th year and could reach a maximum value of $204 million.