Born in Bessemer, Alabama, Bo was originally drafted by the New York Yankees but chose to attend Auburn University from 1982 to 1985 instead, where he was an astounding all-around athlete. At Auburn, Jackson batted .401 with 17 home runs and 43 RBIs in 1985; qualified for the NCAA 60-yard dash finals in his freshman and sophomore years; named the MVP of the 1983 Sugar Bowl, the 1984 Liberty Bowl and the 1986 Cotton Bowl and won the prestigious 1985 Heisman Trophy for his abilities as a running back.

Bo was drafted by the Tampa Bay Buccaneers with the first pick of the 1986 draft, but Jackson opted to play baseball for the Kansas City Royals instead, spending most of the season in the minor leagues before being called up for regular duty in 1987, when he had 22 home runs, 53 RBIs and 10 stolen bases as an outfielder for the Royals. He began to show his true potential in 1989, when he was selected to the American League All-Star team, and was named the game's MVP for his play on both offense and defense. He finished the season by being 4th in the AL in both HRs (32) and RBI (105); in 1990 he raised his batting average as well, but the increasing questions about his football career contributed to a decline in his overall totals.

Following the 1987 baseball season, Jackson decided to again play football (just as a "hobby", he said) and joined the NFL's Los Angeles Raiders, rushing for 554 yards in 81 carries in just seven games. Over the next three seasons, Bo Jackson would rush for 2,228 more yards with 12 touchdowns.

Bo became a popular figure for his athleticism in multiple sports through the late 1980s and early 1990s. Jackson endorsed Nike and launched a popular ad campaign called "Bo Knows" which envisioned Jackson attempting to take up a litany of other sports, including tennis, golf, auto racing, and even blues music with Bo Diddley. In 1990, Bo co-authored his auto-biography, Bo Knows Bo with Dick Schaap. In the book, Bo chronicles his rise from grinding poverty in a family of 10 children to multi-sport, All-Star fame.

During a Raiders playoff game against the Cincinnati Bengals in 1991, Jackson suffered a serious hip injury which ended his football career and seriously threatened his baseball career. Following surgery and rehabilitation on his injured hip, it was discovered that Jackson had avascular necrosis, which caused deterioration of the cartilage and bone around his left hip. Jackson had an artificial hip implanted in 1992, which caused him to miss the entire 1992 baseball season. Many thought that he might never play professional sports again.

However, Jackson was able to return to the Chicago White Sox in 1993, hitting 16 home runs and 45 RBIs; but while his power remained, he no longer had his trademark speed. During his two seasons with the White Sox, Jackson hit only 13 extra-base hits and had no stolen bases. For the 1994 season, Jackson was sent to the California Angels for one final season before retiring.

In 1993, Bo was honored with the Tony Conigliaro Award, given annually to a MLB player who best overcomes an obstacle and adversity through the attributes of spirit, determination and courage that were trademarks of Conigliaro. In 1998, Bo was the fifth Auburn player to be inducted into the National Football Foundation and College Hall of Fame.

Fulfilling a promise he made to his mother before her death in 1992, Bo returned to college and graduated from Auburn University in 1995 with a BS in Human Science. Today, Jackson is a successful businessman living in the Chicago area.