Ryans attended the University of Alabama, where he played outside linebacker for coach Mike Shula's Alabama Crimson Tide football team from 2002 to 2005. Ryans started his career by earning a role on special teams and back up linebacker in his first season. By making great improvements every year in his college career, Ryans went on to become the SEC's Defensive Player of the Year for his performance in 2005. Later on, Ryans attributed much of his college success to his defensive coordinator at Alabama, Joe Kines. He was named the 2006 Cotton Bowl Classic defensive MVP in their 13-10 win over Texas Tech. Following his 2005 senior season, he received the Lott Trophy for his combination of athletic excellence and off-the-field achievements, and was recognized as a unanimous first-team All-American.
Ryans began his NFL career in 2006 with the Houston Texans. Though he had been an outside linebacker in college, he earned the starting middle linebacker position due to his excellent performance in the preseason. In his first game he recorded a league-high 12 solo tackles. Ryans had an overwhelming impact as a rookie linebacker for the Texans, leading the team in tackles in the first half of the 2006 season. Many Texans fans began nicknaming him “D-Wreck” for his toughness and hard hits; other nicknames included D-ROY, intended to promote Ryans for the NFL's Defensive Rookie of the Year award, and "Cap'n Meco," due to his status as a Texans team captain and in reverence of his tremendous professionalism and leadership both on and off the field.
On January 3, 2007, Ryans was awarded the NFL Defensive Rookie of the Year Award after finishing second in the league with 155 total tackles (Zach Thomas 165), 31 more tackles than the next rookie (Detroit Lions linebacker Ernie Sims). He received 36 of 50 votes by a nationwide panel of sports writers and broadcasters. Chicago Bears defensive end Mark Anderson, who was Ryans's teammate at Alabama, finished second with five votes. On December 18, 2007 DeMeco Ryans was selected to the Pro Bowl for the first time. Ryans wore the Texans' defensive transmitter to relay plays from the sideline into the huddle. This meant he was an every-down player. On March 30, 2010, Ryans signed a 6-year $48 million extension, including $21.75 million guaranteed.
On March 20, 2012, after Brian Cushing replaced Ryans as starting middle linebacker, Ryans was traded to the Philadelphia Eagles in exchange for a 2012 fourth-round draft pick and a swap of third-round picks between the two teams. Ryans was immediately inserted as the team's starting Middle Linebacker. On January 4, 2014 he had 10 tackles and his first career playoff interception in his first career playoff games with the Eagles.