He signed with the St. Louis Cardinals afterwards and made his major league debut two days before his 27th birthday. He made an immediate impact, not only scoring 9 triples his rookie year, but also leading the league in sacrifice hits with 26. His 1938 season was not as impressive, but he did manage to increase his batting average over .300. Brown had a career year in , not only leading the league in at-bats with 645, but finishing 6th in MVP voting. He began being known as a reliable leadoff hitter and as an infielder that the Cardinals could put anywhere, having played primarily as a second baseman, as a shortstop, and as a third baseman.
