Born in Titus, Alabama, Sewell lettered in college football at the University of Alabama in 1917, 1918, and 1919. Sewell made his major league debut in 1920 with the World Series champion Cleveland Indians shortly after the death of regular shortstopRay Chapman and became the team's full-time shortstop the following year. An emerging star, Sewell batted .318 with 101 runs, 93 RBI and a .412 on-base percentage in 1921. Sewell's patience and daily work ethic became his hallmarks over the following decade and a half. Playing with Cleveland until 1930 and the New York Yankees from 1931 to 1933, Sewell batted .312 with 1,141 runs, 1,055 RBI, 49 home runs and a .391 on-base percentage. He regularly scored 90 or more runs a season and twice topped the 100 RBI plateau. He hit a career high 11 home runs in 1932.
Of more historical significance, Sewell struck out a mere 114 times in 7,132 career at-bats for an average of one strikeout every 62.5 at-bats, second only to Willie Keeler (63.1). He also holds the single-season record for fewest strikeouts over a full season, with 3, set in 1932. Sewell also had 3 strikeouts in 1930, albeit in just 353 at-bats (as opposed to 503 in his record-setting year), as well as three other full seasons (1925, 1929, 1933) with 4 strikeouts. He struck out ten or more times in only four seasons, and his highest strikeout total was twenty, during the 1922 season. For his 1925–1933 seasons, Sewell struck out 4, 6, 7, 9, 4, 3, 8, 3, and 4 times. He also holds the record for consecutive games without recording a strikeout, at 115.
Sewell also played in 1,103 consecutive games, which to that point was second only to Everett Scott.
His 167.7 at-bats per strikeout in 1932 remains a Major League Single Season record.
According to his obituary published in the New York Times, he played his entire Major League career using only one bat, which he kept in shape by rubbing with a Coke bottle and seasoning with chewing tobacco.
Sewell played in two World Series, in 1920 and 1932, winning both times. His 1977 induction into the Baseball Hall of Fame was by the Veteran's Committee. In 1981, Lawrence Ritter and Donald Honig included him in their book The 100 Greatest Baseball Players of All Time. (He joined the Indians' roster after September 1 in 1920 and normally would not have been eligible to participate in post-season play, but Wilbert Robinson, manager of the Brooklyn Robins, waived the rule because of the circumstances with Chapman.)
Joe Sewell was a member of Pi Kappa Phi fraternity. Sewell-Thomas Stadium, the baseball stadium at the University of Alabama, is named in his honor and is nicknamed by Crimson Tide fans as "The Joe". He served as head baseball coach at his alma mater from 1964 to 1969 and was 106–79 with a .573 overall winning percentage. One of his pitchers was future NFL standout, Alabama quarterback and 1966 MLB 10th round draftee (Yankees) Ken "Snake" Stabler.
Posthumously, Joe Sewell's community (Elmore County) has established a scholarship award recognizing local high school seniors who exhibit Christian character, leadership in their community, strong academic standing, and athletic achievements. Joe Sewell graduated from Wetumpka High School in 1916.