Horton has coached in the NFL for 17 seasons and has been with the Steelers for seven years, the last four as defensive backs coach.
Horton, who played in the NFL for 10 seasons, becomes the Cardinals' third defensive coordinator in Whisenhunt's four years in Arizona. He replaces Bill Davis, who was fired after two seasons on the job.
Horton and the Cardinals met in Arizona on Wednesday to finalize the deal, league sources told ESPN NFL Insider Adam Schefter. Former Steelers defensive back Deshea Townsend is likley to follow Horton as an assistant, sources said.
The Cardinals were reportedly interested in Steelers linebackers coach Keith Butler, but were denied permission to talk to him, the Arizona Republic reported. It was the second time in three seasons the Cardinals had sought Butler.
Whisenhunt was the Steelers' offensive coordinator when he was hired as Arizona head coach in 2007. With the Cardinals, he retained Clancy Pendergast as defensive coordinator but fired him following the team's run to the Super Bowl in the 2008 season.
Horton, 50, worked for 11 years with Steelers defensive coordinator Dick LeBeau, at Cincinnati and with Pittsburgh.
A second-round draft pick out of Washington in 1983, Horton played defensive back for six seasons with Cincinnati and four with the Dallas Cowboys. He played in two Super Bowls, with the Bengals in 1989 and Dallas in 1993.
Horton coached for the Washington Redskins (1994-1996), Cincinnati Bengals (1997-2001) and Detroit Lions (2002-2003) before going to Pittsburgh, where he helped the Steelers reach the Super Bowl three times.
Defense has been a persistent trouble spot for much of Whisenhunt's time in Arizona. The defense showed some improvement in the 2009 season, then surrendered 90 points in two playoff games.
In last year's 6-10 season, Arizona ranked 29th in total defense, 23rd in passing defense and 30th in rushing defense.
Horton is the fourth coach on Arizona's staff who worked with Whisenhunt in Pittsburgh.
Russ Grimm, who carries the complicated title of assistant head coach, running game coordinator and offensive line coach, came to the Cardinals as Whisenhunt's right-hand man after being a finalist for the Arizona head coaching job.
Special teams coach Kevin Spencer and linebackers coach Matt Raich also came with Whisenhunt from Pittsburgh.
Information from The Associated Press was use in this report.