Referred to as both "Bill" and "Willie," as well as "The Shoe", Shoemaker was born in the town of Fabens, Texas. At 2.5 pounds (1 kg), Shoemaker was so small at birth that he wasn't expected to live through the night. Kept in a shoebox in the oven to stay warm, he survived, but remained small, growing to be 4 feet 11 inches (1.50 m) and weighing only 95 pounds (43 kg). His diminutive size proved a benefit as he went on to become a giant in thoroughbred horse racing.

His career as a jockey began in his teen years, with his first professional ride on March 19, 1949. The first of his eventual 8,833 career victories came a month later - on April 20 - on a racer named Shafter V. In 1951, he won the George Woolf Memorial Jockey Award.

Shoemaker won 11 Triple Crown races during his career, but the Crown itself eluded him.

The breakdown of wins is as follows:

Kentucky Derby - Swaps (1955), Tomy Lee (1959), Lucky Debonair (1965) and Ferdinand (1986) Preakness Stakes - Candy Spots (1963) and Damascus (1967) Belmont Stakes - Gallant Man (1957), Sword Dancer (1959), Jaipur (1962), Damascus (1967) and Avatar (1975) Two of Shoemaker's most noted rides during his career were at the Kentucky Derby. He lost the 1957 Kentucky Derby, aboard the mount Gallant Man, when he stood up in the stirrups too soon, having misjudged the finish line. He and Gallant Man ended up finishing second to Bill Hartack aboard Iron Liege. At the 1986 Kentucky Derby, Shoemaker became the oldest jockey ever to win the race (at age 54) aboard the 18-1 outsider Ferdinand. The following year, he rode Ferdinand to a victory over Alysheba in the Breeders' Cup Classic to capture Horse of the Year honors.

As a jockey, The Shoe's most unusual mount was surely the wildly popular California horse, Silky Sullivan. Shoemaker said of Silky, "You just had to let him run his race...and if he decided to win it, you'd better hold on because you'd be moving faster than a train."

When Shoemaker earned his 6,033rd victory in September 1970, he broke the record of jockey Johnny Longden. In 1999, Shoemaker's own record of 8,833 career victories was broken by Panamanian-born Laffit Pincay Jr.

Win #8,833, Shoemaker's last, came at Gulfstream Park, Florida on January 20, 1990 aboard Beau Genius. Two weeks later, on February 3, Shoemaker rode in his very last race as a jockey, at the Santa Anita racetrack. He finished 4th, aboard a horse by the name of Patchy Groundfog. All told, Bill Shoemaker rode in a record 40,350 races.

Soon after retiring as a jockey, Shoemaker returned to the track as a trainer, where he had modest success. A car accident on April 8, 1991 left him paralyzed from the neck down and wheelchair-bound, but he continued to train racehorses until his retirement in 1997.

Shoemaker was inducted into the National Museum of Racing and Hall of Fame in 1958.

The term "shoe-in" or "shoo-in", used to indicate a person who is certain to win some race or contest (particularly in horse racing), is sometimes associated with Shoemaker's name because of the phonetic similaries. The term's use in horse racing actually dates back to the early 1900s .