As a player, Huggins joined the Cincinnati Reds in 1904 as a second baseman. Despite his short stature (5-foot-6-inches), or perhaps because of it, Huggins proved very adept at getting on base. Over a 13-year career which shifted to St. Louis in 1910, he led the league in walks four times and regularly posted an on base percentage near .400. He scored 100 or more runs three times and regularly stole 30 or more bases. He finished his career with 324 swipes.

Huggins became a player-manager for St. Louis in 1913. Although as St. Louis's manager until 1917 he didn't find any substantial success (they never finished higher than 3rd), he was able to build on his experience as the manager of a budding New York Yankee team beginning in 1918. As the Yankees skipper until his death in 1929, and with one of the finest offenses every assembled as his disposal (including Babe Ruth, Lou Gehrig and Bob Meusel), Huggins presided over six American League championships (1921 - 1923, 1926 - 1928) and three World Series championships (1923, 1927 and 1928). He finished his managerial career with a 1413-1134 record. His 1413 wins as a manager ranks 20th all-time.

Huggins died at the age of 50 on September 25, 1929, of blood poisoning brought on by an infection under his right eye. The league cancelled its games for the following day out of respect; the viewing of his casket at Yankee Stadium drew thousands of tearful fans. He was inducted into the Baseball Hall of Fame in 1964.

On May 30, 1932, the Yankees dedicated a monument to Huggins, and placed it in front of the flagpole in center field at Yankee Stadium. This was the first such honor granted by the team, and was the beginning of what would later become "the monuments" and, after the Stadium reopened in 1976 following a two-year renovation, "Monument Park." The monument calls Huggins "A splendid character who made priceless contributions to baseball."