Owens's racing career began after his service in the U.S. Navy, returning in 1946 to compete in the Modified division that would soon be organised under NASCAR. His dominance was staggering: in 1949 he entered 23 races and won 19 of them, and in 1951 he accumulated 54 wins. He put together a string of 24 consecutive victories in 1950–51 and repeated the feat twice more. He won the big modified championship race at Daytona in 1953 and 1954 and claimed the United States Modified Championship three times. He was the Modified champion in 1950, 1953, and 1954.
Owens stepped into NASCAR's Grand National division in 1950. His first Grand National win came on 17 February 1957 at the Daytona Beach Road Course, where he drove a 1957 Pontiac to victory over Johnny Beauchamp by 55 seconds at an average speed exceeding 101 mph — the first race on the beach to average over 100 mph and Pontiac's first NASCAR win.
He registered at least one Grand National victory in each season from 1957 through 1961. In 1959, despite limiting his Grand National starts because the Modified circuit still offered larger crowds and higher purses, he finished second to Lee Petty in the championship standings. His most productive driving season came in 1961, with four wins in 17 starts. He took his final career victory as a driver in 1964, beating David Pearson at Richmond in a brief return from retirement.
As Owens transitioned from driver to car owner, he built a stable of Pontiac and later Dodge machinery from a 20,000 square-foot garage in Spartanburg. Drivers who climbed into his cars during the early 1960s included Fireball Roberts, Junior Johnson, Ralph Earnhardt, and an emerging David Pearson.
In 1963 Owens signed with Dodge as a factory team, fielding cars for Pearson, Billy Wade, Bobby Isaac, Jim Paschal, and others. When Chrysler released the hemispherical combustion chamber engine in 1964, Owens and Pearson capitalised immediately: Pearson won eight times and recorded 29 top-five finishes in 61 starts. Owens himself briefly returned to the cockpit at a Richmond USAC race that year, beating Pearson.
The Chrysler Hemi was banned by NASCAR mid-1965, and Chrysler boycotted the series; Owens and Pearson ran a Hemi-powered Dodge Dart in drag racing that year rather than comply with what they considered an unfair ruling. When the ban was lifted in 1966, Owens and Pearson returned with devastating effect. Pearson won 15 Grand National races in 42 starts, sweeping both races at Hickory, Winston-Salem, and Richmond, and Cotton Owens Garage claimed the NASCAR Grand National Championship. Over six seasons together, the Owens-Pearson partnership produced 27 wins in 170 races.
Owens ran Charger 500 and Charger Daytona aerodynamic variants in the late 1960s with drivers including Buddy Baker and Charlie Glotzbach. Baker won the 1970 Darlington Southern 500 in a Cotton Owens Dodge — a race that had eluded Owens for more than two decades as both driver and owner. Notable drivers who raced for Owens also included Mario Andretti, Al Unser, and country music artist Marty Robbins, whose cars Owens built and maintained until Robbins's death in 1982.
In total, 25 drivers raced for Cotton Owens across 291 starts as an owner, producing 32 victories and 29 pole positions. Combined with his driving career, his total statistics across 487 races stand at 41 wins and 38 poles.
Owens died on 7 June 2012 at the age of 88, having been diagnosed with lung cancer seven years earlier, just weeks after it was announced he would join the NASCAR Hall of Fame's 2013 induction class. He was inducted posthumously. He was also named one of NASCAR's 50 Greatest Drivers in 1998, inducted into the International Motorsports Hall of Fame in 2008, and received the Order of the Palmetto, South Carolina's highest civilian honour, in 2006.