Zach Curlin began coaching the team in 1924, and they joined the Mississippi Valley Conference in 1928. Curlin's last season coaching the Tigers was in 1948, by which time the school had been renamed Memphis State College, and become Memphis State University in 1957. His successor was McCoy Tarry, and John Wallisa became the first Memphis State player to be drafted by the NBA in 1952. In 1954 Forest Arnold became the school's first All-American, and their second was Win Wilfong in 1957. The Tigers made the NCAA tournament for the first time in 1955 under coach Eugene Lambert, and Bob Vanatta became the team's coach in 1956 and took the Tigers to the NIT final.

The team received a number one seed in the 2008 NCAA tournament and defeated 16 seed Texas-Arlington in round one, 8 seed Mississippi State in round two, and 5 seed Michigan State in the sweet sixteen. Memphis won their first Final Four since 1985, after convincingly beating number 2 seed Texas in the Elite 8 round, and following this win, they went on to beat UCLA on April 5, 2008, advancing to the national championship game on April 7, 2008.