He played college football for the Presbyterian Blue Hose and was selected by the Arizona Cardinals in the sixth round of the 2012 NFL draft.

[6] On March 9, 2012, Bethel participated at Presbyterian's pro day and opted to run the 40, 20, and 10-yard dash while also performing positional drills.

He competed with Greg Toler, Michael Adams, Crezdon Butler, A. J. Jefferson, and Jamell Fleming for a backup cornerback position.

Head coach Ken Whisenhunt named him the sixth cornerback on the Arizona Cardinals' depth chart to begin his rookie season, behind Patrick Peterson, William Gay, Greg Toler, Jamell Fleming, and Michael Adams.

On December 23, 2012, Bethel recovered Olindo Mare's blocked field goal and returned it 82-yards for a touchdown in a 28–13 loss to the Chicago Bears.

[16] Bethel entered Arizona Cardinals' training camp in 2013 competing with Antoine Cason, Jerraud Powers, Jamell Fleming, Javier Arenas, and Bryan McCann for the vacant starting cornerback position left by the departure of William Gay.

New Cardinals' head coach Bruce Arians named him the sixth cornerback on the depth chart to begin the season, behind Patrick Peterson, Jerraud Powers, Antoine Cason, Javier Arenas, and Jamell Fleming.

[19] Bethel was selected to be in the 2014 Pro Bowl as a special teams player, joining teammates Patrick Peterson, Antonio Cromartie, and Calais Campbell.

[22] Bethel gave up his number #31 to Antonio Cromartie and switched to #28, which belonged to Rashard Mendenhall the season prior before he retired.

[23] He competed for the starting cornerback job in training camp, going up against Antonio Cromartie, Jerraud Powers, and Brandon Sermons.

Head coach Bruce Arians named Bethel the fourth cornerback on the depth chart to begin 2014, behind Patrick Peterson, Antonio Cromartie, and Jerraud Powers.

[32] Bethel entered training camp competing with Jerraud Powers for the vacant starting cornerback job left by the departure of Antonio Cromartie.

[36] On November 1, he earned his first career start and recorded four solo tackles and two pass deflections in a 34–20 victory against the Cleveland Browns.

[38] He became the starting nickelback for the remainder of the season in Week 16 after safety Tyrann Mathieu tore his ACL and was placed on injured reserve.

[39][40] On December 27, Bethel recorded a career-high eight combined tackles and intercepted a pass attempt by Aaron Rodgers in a 38–8 win over the Green Bay Packers.

[41] He finished the regular season with career highs in tackles (46), passes defended (9), and interceptions (2), as well as two forced fumbles and a touchdown.

[44] On January 16, 2016, Bethel started in his first career postseason game and collected six solo tackles and defended a pass as the Cardinals defeated the Green Bay Packers 26–20 in overtime, winning the NFC Divisional Round.

[47] On April 20, 2016, it was reported that Bethel had undergone surgery earlier in the week to repair slight fracture in his ankle that he had suffered on November 23, 2015, against the Cincinnati Bengals.

[48] Bethel was expected to be the Arizona Cardinal's starting cornerback alongside Patrick Peterson after Jerraud Powers had departed through free agency.

[49] Upon his arrival at training camp, he competed with Mike Jenkins, Asa Jackson, Tharold Simon, and Brandon Williams.

[55] Head coach Bruce Arians named Bethel the starting cornerback, along with Patrick Peterson, to begin the regular season.