In 1978, Horton graduated early from Mount Tahoma High School in Tacoma, Washington, where he was a prep All-American. In 1999, he was named to the second-team defense of the Washington High-School Football Team Of The Century by the Seattle Times newspaper.
Horton accepted a scholarship from the University of Washington, where he played as a cornerback and special teams from 1980 to 1982 after a redshirt year. As a sophomore, he started 9 games. As a junior, he was a first-team All-Pac 10 selection, honorable-mention All-American. In his last year he started 9 games, missing 3 games with an ankle injury (was replaced by Vince Newsome).
He finished as a three-year starter with 10 career interceptions, 22 passes defensed, including 14 (school record) in 1981 and played in two Rose Bowls. He was also one of the top punt returners in the nation.
Horton was selected by the Cincinnati Bengals in the second round (53rd overall) of the 1983 NFL Draft. He also was selected by the Los Angeles Express in the third round (25th overall) of the 1983 USFL Draft.
He earned the job as a starting cornerback by the second game of the season (5 starts) and finished with a franchise rookie record of 5 interceptions. The next year, he was named the regular starter at right cornerback after the retirement of Ken Riley.
In 1986, he was passed on the depth chart by rookie Lewis Billups and was moved to the nickelback role. The next year, he started 8 games, while replacing an injured Louis Breeden.
The Bengals reached Super Bowl XXIII in the 1988 season. After being up 13–6 over the San Francisco 49ers at the beginning of the fourth quarter, driving from the Bengals 10-yard line, quarterback Joe Montana threw a pass towards Billups that he dropped in the end zone. On the next play, the 49ers scored a touchdown, tying the game at 13. Towards the game's conclusion, Montana threw a 10-yard touchdown pass to John Taylor who was being covered by Horton, for a 20–16 lead with 34 seconds left and the eventual championship. He also was the team's punt returner during the game.
On March 14, 1989, the Dallas Cowboys signed Horton as a Plan B free agent with the intention of playing him at safety. He was named the starting free safety and helped anchor the secondary, while becoming the team's second-leading tackler (116). The next year, he posted 69 tackles, 6 passes defensed, one interception and 4 fumble recoveries.
In 1991, he finished third on the team in tackles (105), recorded 8 passes defensed, one interception and scored in back-to-back games. On a fumble return in a 21-16 win against the New York Giants and on a 65-yard interception return in a 20-17 win over the Green Bay Packers.
In 1992, he started the first 7 games before tearing his right ACL (he chose not to have surgery) and missing 4 games. He was replaced with James Washington who took over the starting job. He still was able to be part of the championship team in Super Bowl XXVII.
Horton was released on June 1, 1993, with the Cowboys looking to give more opportunities to Washington and Darren Woodson. He finished his career with 19 interceptions, 11 fumble recoveries, 5 defensive touchdowns.
Horton began his coaching career in 1994 as a defensive assistant with the Washington Redskins. He was hired by Norv Turner, who knew him from Dallas where Turner was an Offensive Coordinator. Horton was the defensive backs coach for the Bengals (1997-01) and Detroit Lions (2002-03). He was the assistant defensive backs coach for the Pittsburgh Steelers from 2004-2006 before being promoted to defensive backs coach in 2007.
On February 9, 2011, Horton was named defensive coordinator for the Arizona Cardinals. In 2013, Arizona head coach Ken Whisenhunt was fired, though Horton was initially retained and considered for promotion to head coach. On January 17, 2013, Horton was passed over for the promotion in favor of his former fellow assistant at Pittsburgh Bruce Arians, leading to his prompt departure from Arizona.
On January 18, 2013, Horton was hired as the defensive coordinator of the Cleveland Browns. On January 18, 2014, Horton agreed to become the defensive coordinator of the Tennessee Titans. Browns coach Hue Jackson hired Ray Horton to be the Browns defensive coordinator going into the 2016 season. After a single season, Horton was fired by the Browns on January 7, 2017.