Considered a three-star recruit by Rivals.com, Matthews was listed as the No. 17 inside linebacker in the nation in 2007. He chose Oregon over offers from Arizona State, California, Colorado, Georgia Tech and Ole Miss.

Matthews attended the University of Oregon where he studied economics. As a true freshman in 2007, Matthews saw action in the first 11 games including one start against Arizona. He recorded 18 tackles including 11 solo. After suffering a shoulder injury late in the season, he did not play in the game against Oregon State or in the 2007 Sun Bowl.

In 2008 he played in all 13 games and recorded 67 tackles, including 13 tackles for loss and two sacks. Matthews compiled a career-high of nine tackles three times, against California, Stanford, and Oklahoma State. He finished as the team’s sixth-leading tackler and third in terms of tackles for loss, with 13.0 for 44 yards. College Football News included him among their “120 Players To Know” and wrote that he is “fundamentally sound, he diagnoses plays well and has a knack for filling the proper lane, a couple of keys to being a successful inside linebacker.” Matthews participated in the 2011 BCS National Championship Game, where Oregon lost to Auburn, 22–19. Matthews recorded a forced fumble against Heisman Trophy winner, Cam Newton, which led to a game-tying score late in the fourth quarter.

Matthews was selected by the Philadelphia Eagles in the fourth round (116th overall) of the 2011 NFL Draft. He was signed to a four-year contract on July 27, 2011. He opened the 2011 NFL season as the Eagles’ starting middle linebacker. He became the Eagles starting nickel-linebacker before the Eagles Week 14 game at Miami. He recorded his first career sack in that same game.

Casey married his high school sweetheart Alyssa Grillo on July 14, 2012. They have two kids together.

Matthews was signed by the Minnesota Vikings as a free agent on March 24, 2015. He sustained a hip labrum injury that required surgery and was placed on injured reserve.