He played college football at the University of Kansas, where he received consensus All-American honors, and was selected by the Tampa Bay Buccaneers in the first round of the 2008 NFL draft.

Against rival Kansas State, Talib preserved a victory by intercepting a Josh Freeman pass in the final moments of the game.

[5] In the 2008 Orange Bowl against Virginia Tech, Talib returned an interception for a touchdown thrown by Tyrod Taylor and was named the game's Most Valuable Player.

[7] As one of the nation's top cornerback prospects, Talib received an invitation to the 2008 NFL Combine, held at the RCA Dome in Indianapolis, Indiana.

Head coach Jon Gruden named Talib the third cornerback on the depth chart behind veteran Ronde Barber and Buchanon to begin the regular season.

In Week 2, Talib made his first career interception off a pass attempt by Atlanta Falcons' rookie quarterback Matt Ryan as Tampa Bay defeated them 24–9.

On October 12, 2008, he recorded a season-high three combined tackles, deflected two passes, and intercepted Jake Delhomme in a 27–3 win over the Carolina Panthers.

[20] On October 4, 2009, Talib recorded four solo tackles, three pass deflections, and had a career-high three interceptions off of Washington Redskins' quarterback Jason Campbell during their 16–13 loss.

[23] Head coach Raheem Morris retained defensive coordinator duties and opted to keep Ronde Barber and Aqib Talib as the starting cornerbacks.

On August 31, 2010, it was reported that the NFL Commissioner Roger Goodell issued Talib a one-game suspension, to serve during the Buccaneers' season-opener, for his involvement in a battery of a taxi driver (See Personal life).

[24] He made his season debut in the Tampa Bay Buccaneers' Week 2 game against the Carolina Panthers and recorded a tackle, a pass deflection, and an interception during their 20–7 victory.

On October 31, 2010, Talib recorded five solo tackles, two interceptions, and scored his first career touchdown in Tampa Bay's 38–35 victory at the Arizona Cardinals.

On December 6, 2010, the Tampa Bay Buccaneers placed Talib on injured reserve due to a hip injury he suffered during a Week 13 loss to the Atlanta Falcons.

On November 27, 2011, Talib recorded three combined tackles, deflected a pass, and scored his third career touchdown after intercepting Matt Hasselbeck and returning it 28-yards during the Buccaneers' 23–17 loss at the Tennessee Titans.

[32][33] He finished the season with 34 combined tackles (31 solo), 11 pass deflections, two interceptions, two touchdowns, and a forced fumble in 13 games and 13 starts.

Head coach Bill Belichick named Talib one of the starting cornerbacks with Kyle Arrington after moving Devin McCourty to free safety.

Without Talib, Kyle Arrington and rookie Logan Ryan were tasked with covering Demaryius Thomas as the Patriots' defense gave up 505 yards, the most during the Belichick's tenure with New England at the time.

[55][56] The New England Patriots also offered Talib a contract, but he stated it was a business decision and both parties could not agree on the amount of guaranteed money and time of payouts.

[57] On October 12, 2014, Talib recorded four solo tackles, two pass deflections, and returned an interception by Geno Smith for a 22-yard touchdown in the fourth quarter of their 31–17 victory at the New York Jets.

The following week, Talib made four combined tackles, tied his season-high of three pass deflections, and returned an interception off Cincinnati Bengals' quarterback Andy Dalton for a 33-yard touchdown in a 37–28 loss.

[60] In Week 17, Talib recorded four combined tackles and made his first career sack on Derek Carr as the Broncos routed the Oakland Raiders 47–14.

Defensive coordinator Wade Phillips chose to keep Talib and Chris Harris Jr. as the starting cornerbacks with Bradley Roby as the nickelback.

[63] He started the Denver Broncos' season-opener against the Baltimore Ravens' and recorded three combined tackles, two pass deflections, and intercepted quarterback Joe Flacco and returned it for a 51-yard touchdown in their 19–13 victory.

On November 8, 2015, Talib poked the eye of Indianapolis Colts tight end Dwayne Allen late in the fourth quarter of the Broncos' 27–24 loss.

On January 24, 2016, Talib tipped a two-point conversion pass by Tom Brady which the Broncos intercepted in the end zone, preserving a 20–18 fourth quarter lead as they defeated the New England Patriots in the AFC Championship.

He got off to a bad start in the game when he was assessed two personal foul penalties in the first half for clashing with wide receiver Corey Brown, first for taunting him after a sack, then for viciously grabbing his face mask to prevent him from scoring a touchdown.

[75] On September 17, 2017, in Week 2 against the Dallas Cowboys, Talib recorded a career-long 103-yard pick six off quarterback Dak Prescott late in the fourth quarter of the 42–17 victory.

[83] On March 8, 2018, the Broncos agreed to a trade that sent Talib to the Los Angeles Rams in exchange for a fifth round pick in the 2018 NFL draft.

He was set to join the Thursday Night Football broadcasting team for Amazon Prime Video, but stepped away from the position due to personal legal difficulties.

[104] In March 2011, police in Garland, Texas, issued a felony warrant for Talib for aggravated assault with a deadly weapon after he was accused of firing a gun at his sister's boyfriend.