Nelson was a two-time first-team All-State honoree, and helped lead Palm Bay to win Florida Class 4A state championship as a safety and return specialist in 2002.

In his junior year, which would end up being his last season as a Gator, Nelson was selected as a member of the team's Leadership Committee, which was only one small highlight of his 2006 campaign.

The Gators ended up going to the BCS National Championship Game and defeated the Ohio State Buckeyes, while Nelson recorded fifty-one tackles, five pass breakups and six interceptions.

He finished his rookie season with 63 combined tackles (58 solo), 11 pass deflections, five interceptions, and a forced fumble in 16 games and 15 starts.

[21] The Jacksonville Jaguars hired Gregg Williams to be their new defensive coordinator after Mike Smith accepted the head coaching role with the Atlanta Falcons.

[20] Throughout training camp in 2010, Nelson competed for a role as a starting safety against Anthony Smith, Gerald Alexander, and Sean Considine.

[28] On September 4, 2010, the Jaguars traded Nelson to the Cincinnati Bengals in exchange for cornerback David Jones and a conditional draft pick.

[29] Head coach Marvin Lewis named Nelson the backup free safety, behind Chris Crocker, to start the regular season.

[30] On October 31, 2010, Nelson earned his first start with the Bengals after Roy Williams and Chinedum Ndukwe were listed as inactive due to knee injuries.

On November 22, 2010, Nelson became the starting free safety after the Cincinnati Bengals placed Chris Crocker on injured reserve for the remainder of the season due to a torn ACL.

On December 26, 2010, Nelson collected a season-high eight combined tackles and a pass deflection in the Bengals' 34–20 victory against the San Diego Chargers in Week 16.

Nelson finished his first season with the Cincinnati Bengals with 54 combined tackles (34 solo), seven pass deflections, and two interceptions in 16 games and six starts.

[33] Defensive coordinator Mike Zimmer officially named him the starter to begin the regular season, alongside free safety Chris Crocker.

[34][35] He started in the Cincinnati Bengals' season-opener at the Cleveland Browns and recorded nine combined tackles, two pass deflections, and a sack in their 27–17 victory.

[36] In Week 8, Nelson recorded five solo tackles, two pass deflections, and returned an interception for his first career touchdown in the Bengals' 34–12 victory at the Seattle Seahawks.

[36] He intercepted a pass by quarterback Tarvaris Jackson that was originally intended for wide receiver Kris Durham and returned it for a 75-yard touchdown with 49 seconds left in the fourth quarter.

[37] On December 24, 2011, he made seven combined tackles, a pass deflection, a sack, and an interception in the Bengals' 23–16 win against the Arizona Cardinals in Week 16.

[36] Nelson finished the 2011 season with 85 combined tackles (59 solo), 12 pass deflections, four interceptions, two sacks, two forced fumbles, and a touchdown in 16 games and 16 starts.

On January 7, 2012, Nelson collected six combined tackles and sacked quarterback T. J. Yates during a 31–10 loss at the Houston Texans in the AFC Wildcard Game.

[43] On October 7, 2012, Nelson tied his season-high of ten combined tackles (five solo) in the Bengals 17–13 loss to the Miami Dolphins in Week 5.

[43] In Week 9, Nelson made five combined tackles and broke up a pass before exiting the Bengals' 31–23 loss to the Denver Broncos in the third quarter after injuring his hamstring.

On January 6, 2013, Nelson started in the AFC Wildcard Game and recorded ten combined tackles (nine solo) in the Bengals' 19–13 loss at the Houston Texans.

[20] The Cincinnati Bengals hired Paul Guenther as their new defensive coordinator after Mike Zimmer accepted the head coaching position with the Minnesota Vikings.

[20] On October 18, 2015, Nelson recorded a season-high 12 combined tackles (eight solo) and broke up a pass during a 34–21 win at the Buffalo Bills in Week 6.

On January 9, 2016, Nelson started in the AFC Wildcard Game and recorded three combined tackles and a sack before exiting in the third quarter of the Bengals' 18–16 loss to the Pittsburgh Steelers with an ankle injury.

[62] He started in the Oakland Raiders' season-opener at the Tennessee Titans and recorded a season-high eight combined tackles and a pass deflection in their 26–16 victory.

On December 25, 2017, Nelson recorded six solo tackles, a season-high three pass deflections, and an interception in the Raiders' 19–10 loss at the Philadelphia Eagles in Week 16.

Nelson's mother, Mary Lakes, who had breast cancer for several years, died on December 21, 2006, weeks before the 2007 BCS National Championship Game.