The product of a baseball family, Molina was born in Bayamon, Puerto Rico. His father was an amateur second baseman and the all-time hits leader in Puerto Rican baseball, and his two older brothers, Bengie and José, also developed into standout defensive catchers with lengthy MLB careers. Long before playing professionally, Molina's pitch-handling and throwing skills caught the attention of scouts. The Cardinals' fourth-round selection in the 2000 MLB draft, he quickly showed one of the strongest and most accurate arms in the game after starting play in the major leagues. Having earned a reputation as a team leader throughout his career, Molina formulates fielder positioning plans and complete pitching strategies to opposing hitters. At the end of the 2020 season, Molina was the longest-tenured player in Major League Baseball with one team, having been with the Cardinals since the middle of the 2004 season.