He played professionally in the NFL for 11 seasons as a running back, primarily with the Buffalo Bills from 1969 to 1977.He also played for the San Francisco 49ers from 1978 to 1979.In 2007, Simpson was arrested in Las Vegas, Nevada, and charged with the felonies of armed robbery and kidnapping.

In 1973, he became the first NFL player to rush for more than 2,000 yards in a season.

He holds the record for the single season yards-per-game average, which stands at 143.1.

Despite Simpson's performance, the Bills would lose the game 27–14.

Simpson gained 11,236 rushing yards, placing him 2nd on the NFL's all-time rushing list when he retired; he now stands at 21st.

After retiring from football, he began new careers in acting and football broadcasting.

In 1994, Simpson was arrested and charged with the murders of his ex-wife Nicole Brown Simpson and her friend Ron Goldman.

He is the only player to ever rush for over 2,000 yards in the 14-game regular season NFL format.

Simpson was inducted into the College Football Hall of Fame in 1983 and the Pro Football Hall of Fame in 1985.

He was acquitted by a jury after a lengthy and internationally publicized trial.

The families of the victims subsequently filed a civil suit against him, and in 1997 a civil court awarded a .5 million judgment against Simpson for the victims' wrongful deaths.

As a child, Simpson developed rickets and wore braces on his legs until the age of five, At Galileo High School (currently Galileo Academy of Science and Technology) in San Francisco, Simpson played for the school football team, the Galileo Lions.