He was signed by the minor league Atlanta Crackers in 1930 and debuted with the Chicago White Sox later that year.

The Chicago Cubs showed some interest at first, but decided not to sign him, and the White Sox ended up purchasing him from the Crackers for $20,000.

He finished second in the AL Most Valuable Player voting and earned his first All-Star Game selection.

[3] Appling missed the entire 1944 season due to military service in the United States Army, then returned in time to appear in only 18 games the next year.

[3] Appling had remained a solid contributor into his forties, but White Sox ownership was dedicated to a youth movement and he retired after the 1950 season.

Charlie Metro testified to this reputation: "The old White Sox shortstop Luke Appling was a delight.

"[5] Appling was famous among his teammates for complaining about minor ailments such as a sore back, a weak shoulder, shin splints, or a sprained finger.

[6] "His constant stream of complaints might have become intolerable to his teammates if Appling had not developed a novel remedy," wrote Robert McG.

Beginning in 1954, he managed the unaffiliated Richmond Virginians, a Class AAA team in the International League which affiliated with the New York Yankees in 1958 but after 1964 moved and became the Toledo Mud Hens.

Appling was a major league coach for the Cleveland Indians, Detroit Tigers, Baltimore Orioles, Athletics and White Sox during the 1960s and early 1970s.

[8] Though Appling received only two Baseball Hall of Fame votes when he appeared on the ballot in 1953, he was eventually elected in 1964.

[9] In 1970, the Chicago chapter of the Baseball Writers' Association of America named Appling the greatest player in the history of the White Sox.

[8] In 1981, Lawrence Ritter and Donald Honig included him in their book The 100 Greatest Baseball Players of All Time.

On July 19, 1982, Appling played in the initial 1982 Cracker Jack Old Timers game (1982-1990) at Robert F. Kennedy Memorial Stadium in Washington, D.C., where the then 75-year-old Hall of Fame shortstop hit a home run off Warren Spahn in the first inning into the left field bleachers, the ball having traveled 265 feet.

[10] On January 3, 1991, two days after retiring from the Atlanta coaching staff, Appling was in a hospital in Cumming, Georgia, suffering from an abdominal aortic aneurysm.

[7] "Old Aches and Pains" was interred in Sawnee View Memorial Gardens, Mausoleum Chapel West in Cumming, Georgia.

In 2013, the Bob Feller Act of Valor Award honored Appling as one of 37 Baseball Hall of Fame members for his service in the United States Army during World War II.