Rod Woodson attended R. Nelson Snider High School in Fort Wayne, Indiana. He played defensive back and a variety of offensive skill positions and was all-state his junior and senior seasons. in addition to football, he won both the high and low hurdles state championships in both his junior and senior seasons; and played varsity basketball his junior and senior seasons, making all conference his senior year.

In 1987, Woodson was drafted by the Pittsburgh Steelers as the 10th overall draft pick. He returned punts and played defensive cornerback for Pittsburgh through the 1996 season.On November 22, 1987 he was listed third on the depth chart in a game against the division rival Cincinnati Bengals played at Cincinnati’s Riverfront Stadium, Woodson was inserted into the secondary. In the final minute of the second quarter, he recorded his first career interception when he picked off a Boomer Esiason pass.

He was a fan favorite and a banner that hung for years in Three Rivers Stadium stated: "Rod Is God". A highlight came in 1995 when Woodson became the first player to return from reconstructive knee surgery in the same season. That year he tore his ACL against the Detroit Lions in the first game and returned to play in the Super Bowl XXX between the Steelers and the Dallas Cowboys just 19 weeks later. In that game, he broke up a pass intended for Michael Irvin, hopped up and pointed at his reconstructed knee. In a game against the Houston Oilers, Woodson hit Hall of Fame quarterback Warren Moon on a cornerback blitz. The hit gave Moon a concussion and forced him to leave the game.

Woodson's career took a somewhat nomadic turn after free agency from Pittsburgh, after the Rooney family elected not to renew his contract over a pay dispute as well as the salary cap. Although he remained to raise his family in Pittsburgh and later made amends with the Rooneys, he hopped between three additional franchises, becoming one of the few modern cornerbacks to successfully make a transition to the safety position, following in the footsteps of Ronnie Lott. Woodson signed with the San Francisco 49ers for the 1997 season, the Baltimore Ravens for the years 1998 to 2001 (where he won Super Bowl XXXV), and the Oakland Raiders for 2002 and 2003 (where he appeared in his third Super Bowl). In the Raiders 2002 Super Bowl season, 37-year old Woodson led the NFL in interceptions (8) for the first time in his career. His last interception came on November 16, 2003 against the Minnesota Vikings’ Daunte Culpepper.

Rod Woodson is among the NFL's all time leaders in games played as a defensive back and interceptions. In his 17 NFL seasons, Woodson recorded 71 interceptions, 1,483 interception return yards, 32 fumble recoveries (15 offensive and 17 defensive), 137 fumble return yards, 4,894 kickoff return yards, 2,362 punt return yards, and 17 touchdowns (12 interception returns, 1 fumble return, 2 kickoff returns, 2 punt returns). He holds the league record for interceptions returned for touchdowns with 12, and is tied with 11 other players for the record for most fumble recoveries in a single game (3). His 1,483 interception return yards are also an NFL record. His 71 interceptions rank 3rd all time.

Woodson was named to the Pro Bowl eleven times, a record for a defensive back. He was also the first player to earn trips to the Pro Bowl at cornerback, safety and kick returner. He was also a 7 time All-Pro selection. Woodson finished second to Darrell Green in the 1988 NFL Fastest Man Contest.

In 1994, he was named to the NFL's 75th Anniversary Team. What made it notable was that Woodson was one of only five active players to be named to the team. The others were Jerry Rice, Joe Montana, Reggie White and Ronnie Lott. In 1999, he was ranked number 87 on The Sporting News' list of the 100 Greatest Football Players. The College Football News has also honored him as one of the 100 greatest players of the 20th century.

Since 1994, Woodson has operated an annual youth football camp, the Woodson/Fabini Football Camp, on the grounds of his former high school. He is also a partner in Woodson Motorsports, a BMW motorcycle dealership and repair shop in Fort Wayne.

Currently Woodson splits his time between NFL Network studios in Los Angeles, his home in Pleasanton,and his cottage in Coldwater, Michigan. He was also part of the studio team for BBC Sport's NFL coverage in 2007, including Super Bowl XLII and Super Bowl XLIII.