[2] Clements excelled at both defensive back and quarterback and was named an All-American by USA Today, Blue Chip Illustrated and Super Prep.

[10][11] Head coach Gregg Williams named Clements the third cornerback on the depth chart to begin the regular season, behind Antoine Winfield and Ken Irvin.

[13] He made his professional regular season debut in the Buffalo Bills' season-opener against the New Orleans Saints and recorded one solo tackle in their 24–6 loss.

On September 23, 2001, Clements made one tackle, deflected a pass, and returned his first career interception for a touchdown during their 42–26 loss at the Indianapolis Colts.

In Week 8, Clements collected three combined tackles, deflected a pass, and returned a punt for a 66-yard touchdown during the second quarter of a 30–24 loss to the Indianapolis Colts.

[15] In Week 14, he collected three combined tackles and made his first career sack on quarterback Tom Brady during a 12–9 loss at the New England Patriots.

[17] He completed his rookie season in 2001 with 63 combined tackles (53 solo), ten pass deflections, three interceptions, three forced fumbles, a sack, and a touchdown in 16 games and 11 starts.

[20] In Week 12, Clements collected a season-high ten combined tackles (eight solo) and broke up a pass in the Bills' 31–13 loss at the New York Jets.

[21] Clements finished his second season with 65 combined tackles (52 solo), 13 pass deflections, a career-high six interceptions, and a touchdown 16 games and 16 starts.

The Buffalo Bills' new head coach Mike Mularkey retained Clements as a starting cornerback to begin the season, along with newly acquired free agent Troy Vincent.

On November 21, 2004, Clements recorded five combined tackles, broke up a pass, and returned a punt for a touchdown for the first time in his career during a 37–17 victory against the St. Louis Rams.

[27] In Week 17, he recorded five solo tackles, a pass deflection, and returned an interception by rookie quarterback Ben Roethlisberger for a 30-yard touchdown in the Bills' 29–24 loss to the Pittsburgh Steelers.

He completed the 2004 season with 73 combined tackles (53 solo), seven pass deflections, a career-high six interceptions, a touchdown, and was credited with half a sack in 16 games and 16 starts.

In Week 14, he tied his season-high of 11 combined tackles (nine solo), deflected a pass, and made an interception in the Bills' 35–7 loss to the New England Patriots.

[35] He finished the season with 70 combined tackles (54 solo), a career-high 16 pass deflections, three interceptions, two forced fumbles, and a touchdown in 16 games and 16 starts.

[38] On November 25, 2007, Clements collected a season-high ten combined tackles (eight solo) and a pass deflection during a 37–31 victory at the Arizona Cardinals in Week 13.

[38] Clements finished the season with 92 combined tackles (77 solo), 14 pass deflections, four interceptions, three forced fumbles, and a sack in 16 games and 16 starts.

[40] On October 19, 2008, he recorded five combined tackles, a pass deflection, and returned a blocked field goal for a touchdown during the 49ers' 29–17 loss to the New York Giants.

Clements recovered the ball and returned it 74-yards for a touchdown in the third quarter after linebacker Manny Lawson blocked a field goal attempt by Giants' kicker John Carney.

[40] Clements finished the 2008 season with 63 combined tackles (56 solo), nine passes defensed, two interceptions, and a forced fumble in 15 games and 15 starts.

[44] On September 27, 2009, Clements recorded four combined tackles and returned a blocked field goal for a touchdown in the 49ers' 27–24 loss at the Minnesota Vikings.

Clements recovered the ball and returned it for a 59-yard touchdown after it kicker Ryan Longwell's attempt was blocked by Ray McDonald in the second quarter.

[45] He joined Kevin Ross as the only players in NFL history return a blocked field goal for a touchdown on two separate occasions.

Many media members called into question head coach Mike Singletary's decision to place Clements in the punt return role due to his substantial contract and importance in the secondary.

[52] Clements entered training camp slated as a starting cornerback, but saw competition from Terence Newman, Jason Allen, Adam "Pacman" Jones, and Dre Kirkpatrick.

[54] Upon returning, Clements began to transition to strong safety after losing his starting cornerback job to Terence Newman during his absence.