[6][7] Head coach Dennis Green named Rolle a starting cornerback to begin the regular season, alongside David Macklin.

[8] He made his professional regular season debut and first career start in the Arizona Cardinals' season-opener at the New York Giants and recorded one tackle in their 42–19 loss.

During the game, Rolle sustained an injury that was believed to be cartilage damage in his left knee and was scheduled to undergo surgery and miss 3–4 weeks.

On October 3, 2005, Dr. John Uribe performed arthroscopic surgery on Rolle's knee to ostensibly repair the meniscus cartilage, but discovered ligament damage that was expected to sideline him for the rest of his rookie season.

[10] On December 11, 2005, Rolle recorded a solo tackle, a pass deflection, and made his first career interception in the Cardinals' 17–13 loss to the Washington Redskins.

His interception came off a deflection by tight end Chris Cooley who was unable to secure a pass thrown by quarterback Mark Brunell in the second quarter.

[15] On December 17, 2006, Rolle recorded a season-high 11 combined tackles (nine solo) and broke up a pass during a 37–20 loss to the Denver Broncos in Week 15.

[15] He finished the season with 84 combined tackles (77 solo), ten passes defensed, two forced fumbles, and an interception in 16 games and 16 starts.

[17] Rolle entered training camp slated as a starting cornerback, but saw competition for his role from Eric Green and Roderick Hood.

On August 18, 2008, Rolle had a disappointing performance and gave up a 39-yard touchdown reception to wide receiver Andre Johnson during a 33–20 loss to the Houston Texans in their second preseason game.

[18] Two days later, head coach Ken Whisenhunt announced that Roderick Hood would be replacing Rolle as the starting left cornerback after performing well during the preseason.

[19] Head coach Ken Whisenhunt officially announced Rolle as the third cornerback on the depth chart, behind Eric Green and Roderick Hood, to start the regular season.

On November 18, 2007, Rolle recorded four combined tackles, three pass deflections, three interceptions, and returned two for touchdowns during a 35–27 win at the Cincinnati Bengals.

On February 27, 2008, it was reported that the Arizona Cardinals would be moving Rolle to free safety for the 2008 NFL season after he impressed as the nickelback in 2007.

Rolle entered training camp slated as the de facto starting free safety after the Cardinals opted to release Terrence Holt during the offseason.

On November 2, 2008, Rolle recorded four solo tackles, deflected a pass, and returned an interception by Marc Bulger for a 40-yard touchdown during the second quarter of a 34–13 win at the St. Louis Rams in Week 9.

[27] In his first season as a free safety, Rolle recorded 89 combined tackles (78 solo), five passes defensed, an interception, and a touchdown in 16 games and 16 starts.

[27] On February 1, 2009, Rolle started in Super Bowl XLIII and recorded three combined tackles as the Cardinals lost 27–23 in a closely contested matchup against the Pittsburgh Steelers.

[31] In Week 10, he collected a season-high nine solo tackles, made two pass deflections, and an interception in the Cardinals' 31–20 victory against the Seattle Seahawks.

[32] Head coach Ken Whisenhunt chose to rest Rolle during a Week 17 loss to the Green Bay Packers after the Cardinals finished first in their division and clinched a playoff berth with a 10–5 record.

[13] On January 10, 2010, Rolle recorded a season-high 13 combined tackles (nine solo) during a 51–45 victory against the Green Bay Packers in the NFC Wildcard Game.

On October 17, 2010, Rolle recorded six combined tackles, broke up a pass, and made his first interception as a member of the Giants during a 28–20 victory against the Detroit Lions in Week 6.

On January 8, 2012, Rolle recorded nine combined tackles as the Giants routed the Atlanta Falcons 24–2 in the NFC Wild Card Game.

[41] On February 5, 2012, Rolle recorded three solo tackles as the New York Giants defeated the New England Patriots 21–17 to win Super Bowl XLVI.

[42] Rolle entered training camp slated as the starting free safety after the Giants added depth and signed Aaron Ross, Terell Thomas, and Jayron Hosley.

[48] Head coach Tom Coughlin officially named Rolle the starting strong safety to begin the regular season, alongside Mundy.

[49][50] On October 21, 2013, Rolle made a season-high three pass deflections, six combined tackles, and an interception during a 23–7 win against the Minnesota Vikings in Week 7.

Defensive coordinator Perry Fewell chose to retain Rolle as the starting strong safety after he earned a Pro Bowl selection the previous season.

[56][57] Throughout training camp, Rolle competed to be the starting strong safety against former New York Giants' teammate Ryan Mundy.