George was born in Philadelphia, Pennsylvania. He attended Abington Senior High School until the tenth grade, and then transferred to Fork Union Military Academy. George made the decision to stay at Fork Union Military Academy for a fifth prep school year. Such choices are commonly made by high school football players hoping to improve their recruitment status with colleges, but for George it meant another year of the vigorous military lifestyle. George went on to rush for 1,372 yards in his fifth season at FUMA, attracting the attention of several major colleges.
George attended Ohio State University, where he majored in landscape architecture and played for the Ohio State Buckeyes football team. As a freshman running back for the Buckeyes, George was an instant contributor. He scored three rushing touchdowns in a win over Syracuse University. However, he suffered a major setback in a game against the University of Illinois. In that game, George lost a fumble at the Illinois' 4-yard line that was returned 96 yards for a touchdown. Later in the game, with Ohio State leading by 2 points in the final quarter, George fumbled again, this time on Illinois' 1-yard line. Illinois recovered the fumble and drove for the game winning touchdown.
Before the Illinois game, George had carried the ball 25 times and scored 5 touchdowns, but for the rest of the season, he had only 12 more rushing attempts and didn't score once. In the following season, George was used as the team's third string running back, behind Raymont Harris. He carried the ball only 42 times, mostly when Ohio State had a large lead late in games. However, as a junior, George became the team's starting running back and went on to rush for 1,442 yards and 12 touchdowns.
As a senior in the 1995 season, George rushed for a school record 1,927 yards and 24 touchdowns, an average of 148.23 yards per game, while also catching 44 passes for 399 yards and another score (George only caught 16 passes in his first three seasons). One of his best performances of the year was in a 45-26 win over the University of Notre Dame, where he rushed for 207 yards, his third 200-yard game of the season. He also rushed for a school-record 314 yards and scored 3 touchdowns in OSU's victory over Illinois. In the 3 years since committing his 2 fumbles in the Illinois game as a freshman, George had over 600 rushing attempts and fumbled only 6 times. Ohio State finished the season with a 10-2 record, and George was recognized as a consensus first-team All-American and won the Heisman Trophy in the closest vote in the history of the award at the time, beating the University of Nebraska's Tommie Frazier by 264 votes. George left Ohio State second in school history in career rushing yards (3,768) and third in rushing touchdowns (44). Overall, he finished with 4,284 all-purpose yards, 45 touchdowns, and a 5.5 yards per carry average.
George was the first-round draft selection (14th overall pick) of the Houston Oilers (now the Tennessee Titans) in 1996 NFL Draft. George won the NFL Rookie of the Year award in 1996, and was the Oilers/Titans' starting tailback through 2003, never missing a start. He made the Pro Bowl four consecutive years (1997–2000), and assisted the Titans to a championship appearance in Super Bowl XXXIV, where they lost to the St. Louis Rams 23-16. George gained 391 combined rushing and receiving yards in the Titans' three playoff games that year and went on to rush for 95 yards, catch two passes for 35 yards, and score two touchdowns in the Super Bowl.
Though George rushed for 1000 yards in all but one season with Tennessee, numerous sports writers suggested that a heavy workload caused a decline in George's productivity. In five of his eight seasons with the Titans, George carried the ball over 330 times. In 2001, George averaged just 2.98 per carry, the fourth lowest number in league history among running backs with more than 200 rushing attempts in a season. George's decline in production along with numerous toe and ankle injuries were contributing factors in Titans owner Bud Adams' decision to release him after George would not agree to a pay cut.
George signed a one-year contract with the Dallas Cowboys on July 23, 2004 for $1.5 million plus incentives that could have earned him more than the $4.25 million he would have made under his contract with the Titans, who released him on July 21, 2004 in part due to salary cap considerations. George only started 8 games for Dallas, rushing for 432 yards on 132 carries. He retired from the NFL before the 2005 season.
His career totals include 10,441 rushing yards, 268 receptions, 2,227 receiving yards, and 78 touchdowns (68 rushing and ten receiving).
George served as a pre-game analyst for the 2007 BCS Championship Game on FOX, and is well known for handing out OSU hats and apparel to fellow analysts during the Buckeyes' 41–14 loss to the University of Florida. He could be seen cheering on the sidelines during most of the game.
George's mother changed her schedule as a flight attendant (at the request of Eddie's agent, Lamont Smith) to be in San Antonio for Eddie's signing of his first NFL contract on July 19, 1996. If she hadn't, she would have been aboard TWA Flight 800, which crashed shortly after takeoff two days earlier.
With partners, George has opened sports-themed restaurants in Nashville, Tennessee (Eddie George Sports Grille) across the Cumberland River from Nissan Stadium and in Columbus, Ohio (Eddie George's Grille 27) near the Ohio State University campus. George is also a principal of The Edge Group, a planning and landscape architecture firm of over 20 professionals.
In 1995, George's Heisman Trophy was damaged when he put it through an X-ray machine at a New York airport. On October 1, 2006, George was appointed spokesperson for Tennessee's GetFitTN program by Gov. Phil Bredesen. The initiative is aimed at the prevention of Type 2 diabetes and the promotion of healthier, more active lifestyles. On Saturday, April 28, 2007, George ran the Country Music Half Marathon (ending just outside then LP Field, now Nissan Stadium) in an unofficial time of 2:04:08. He wore race number 27 during the race, just as he wore number 27 during his college and NFL careers. George later stated that completing the race was tougher than playing in the NFL. In 2008, George campaigned for SenatorBarack Obama's presidential bid.