Rondón signed with the St. Louis Cardinals as an international free agent on January 6, 2016. He made his professional debut that year with the Rookie-level Dominican Summer League Cardinals, going 2–2 with a 2.79 ERA over 42 innings. In 2017, he played with the Dominican League Cardinals, the Rookie-level Gulf Coast League Cardinals, and the Johnson City Cardinals of the Rookie-level Appalachian League, going a combined 3–4 with a 3.14 ERA over 14 games (11 starts) between the three clubs. He spent 2018 with the State College Spikes of the Class A Short Season New York–Penn League and the Peoria Chiefs of the Class A Midwest League, posting a 3–6 record and a 3.17 ERA over 15 starts with both teams, striking out eighty batters over 88 innings, and 2019 with the Palm Beach Cardinals of the Class A-Advanced Florida State League (where he was named an All-Star) and the Springfield Cardinals of the Class AA Texas League, pitching to an 11–7 record, a 2.93 ERA, and 159 strikeouts over 160 innings and 28 starts with both clubs. Following the season, the Cardinals named Rondón their Minor League Pitcher of the Year.