In 2003, his senior season at Utah State, Cooley led the NCAA in receptions by a tight end.

In 2004, Cooley was drafted in the third round, with the 81st overall pick, of the 2004 NFL Draft by the Washington Redskins. After being used sparingly in the first half of the 2004 season, Cooley began to be used more extensively in the last eight games, developing a rapport with Redskins quarterback Patrick Ramsey. In his first NFL season, Cooley led the team in touchdowns with six, while recording 37 receptions for 314 yards, catching three passes of more than twenty yards, and getting 23 first downs. He finished the season with an average of 8.5 yards per catch. He was the Redskins’ nominee for the NFL Man of the Year award for his work reading to children and feeding the poor. He is also lesser known by the nickname “Johnny White Guy,” which was given to him by Clinton Portis during one of Portis’ colorful press conferences, but the off color nickname did not stick.

During the 2005 season, Cooley had a solid season as a receiver, catching 71 passes for 774 yards and seven touchdowns, including three in a game versus the rival Dallas Cowboys, breaking the Redskins franchise record for receptions as a tight end in a single season. Those three touchdowns cost Cooley his fantasy football playoff game, because his opponent had Cooley on his fantasy team. He led all NFC tight ends in fan voting for the annual Pro Bowl with 422,314 votes, but following player and coach voting (each group had 1/3 weight), was not chosen for the position. He was named first team All-NFC by Pro Football Weekly.

Though he has previously attended The Church of Jesus Christ of Latter-day Saints, he has not affiliated with that Church since at least 2004. He and his first wife Angela divorced in 2005. Later that year, he started dating Redskinnette (Redskin cheerleader) Christy Oglevee. She was fired for fraternizing with Redskins players, which the Redskins organization prohibits. They married on May 23, 2008 in Landsdowne, Virginia. In January 2012 they separated and in September they announced their intent to divorce. Cooley’s first child, daughter Sloane, was born on September 11, 2014.

In 2006, Cooley got off to a slow start under the play-calling of the Washington Redskins’ new offensive coordinator, Al Saunders. With only three receptions in the first two weeks of the season, Cooley appeared to not have a place in the new offensive scheme, but in the weeks following, became a growing part of the Redskins offense. He ended the season with numbers slightly less than his sophomore outing, but was still one of the top tight ends in the game.

On September 1, 2007, Cooley signed a six-year, $30 million contract extension. In 2007, he had scored in all but one game as of week six. In the sixth week, Cooley had nine receptions for a career-high 105 yards and one touchdown in a 17-14 loss against the Green Bay Packers. On December 18, he was named to the 2007 Pro Bowl team with Redskins tackle Chris Samuels, long-snapper Ethan Albright, and the late safety Sean Taylor. Cooley set an NFL record by being the only tight end in league history to have six or more touchdowns in each of his first four seasons.

In 2008, Cooley scored only one touchdown. In Week 5, he had eight receptions for a career-high 109 yards and one touchdown, on a pass from Antwaan Randle El in a 23–17 win against the Philadelphia Eagles. Cooley finished the season with 83 catches for 849 yards and one touchdown, with career highs in both catches and yardage. He was the only player not to get into the stat book in the 2009 Pro Bowl.

Cooley broke his ankle in a Monday Night Football matchup against the Philadelphia Eagles on October 26, 2009. It was initially speculated that Cooley would miss the remainder of the 2009 season. On October 27, 2009, Cooley commented via Twitter that the break may not have been as bad as originally thought and that he could possibly return in as little as four weeks. His longest play of the year was a 66-yard touchdown. On November 30, 2009, Cooley was placed on injured reserve.

Cooley is executive producer of the independent film Ghosts Don’t Exist, which began production in May 2009. He was featured in an episode of Jake and Amir for the comedy website CollegeHumor.

Cooley played in all sixteen games of the 2010 season, but had arthroscopic surgery on his left knee after the season on January 3, 2011.

Still recovering from the arthroscopic surgery to his left knee, Cooley did not play in any of the preseason games in 2011. Cooley played only in the 2011 season’s first five games. After the win in Week 1 against the New York Giants, Cooley became the Washington Redskins’ all-time leader in receptions at the tight end position with 422 receptions, breaking the previous franchise record of 421 set by Jerry Smith. In Week 3 against the Dallas Cowboys, Cooley subbed in for Darrel Young and Mike Sellers, who were both injured, and played the fullback position for the first time in his career. In Week 6 against the Philadelphia Eagles, Cooley suffered a broken finger. On October 25, 2011, Cooley was placed on injured reserve after his knee was examined further by his doctor and he was told that it would take another four or five weeks before full recovery.

During the preseason, it was reported that Cooley’s knee was completely healed from the surgery and that he even lost 20 pounds to prepare for the 2012 season. However, Cooley was released by the Redskins on August 28, 2012. It had been hinted by general manager Bruce Allen that Cooley could return to the Redskins.

On October 21, 2012, Cooley agreed to re-sign with the Redskins after Fred Davis tore his Achilles tendon and was done for the season.

On July 16, 2013, The Washington Post reported that Cooley was retiring from the NFL. The Post further reported that Cooley would join the Washington Redskins’ radio broadcast team as an analyst.

On August 11, 2015, it was reported that Cooley expressed interest into returning to the NFL after working out at the Redskins facility during the off season. Cooley never officially retired from the NFL after not being re-signed by the Redskins in 2013. After playing only with the Redskins throughout his entire career, he was afraid to tarnish his legacy by joining another team. The following month, Cooley attended a workout for the New York Giants but was not signed.

In 2017 he was inducted into the Utah State University Athletics Hall of Fame.

Cooley also co-hosted “Cooley & Kevin”, a morning drive time sports show on ESPN 980 in D. C., with Kevin Sheehan. The show was cancelled in 2018. Cooley now hosts his own podcast, The Chris Cooley Show, in which he discusses Redskins and NFL news and breaks down each week’s game film. He also produces weekly film review segments on the Redskins’ official website.