He first starred at the University of Louisiana at Lafayette (then named Southwestern Louisiana Institute or SLI) from 1922–1925, where he earned a degree in arts and sciences. In his career at Louisiana-Lafayette, he scored 235 points from touchdowns, extra points and field goals, a school record that lasted until 1989. His time at Louisiana Lafayette has him placed among the all-time greats of early Southern football. Besides being the football captain (1925), he also was a star in basketball and track and field sports at Louisiana-Lafayette, where he received a degree in arts and sciences.
Cagle then played college football for four years at the United States Military Academy (Army) 1926–1929 but did not graduate because he had secretly married in August 1928 in violation of Academy rules. He was forced to resign in May 1930. Known as the "Red Thunderbolt of West Point," he was an All-American halfback for the last three years. His longest runs were 75 yards against Yale, 1928; 70 yards against Ohio Wesleyan and 65 yards against Yale, 1929. In four years at Army he scored 169 points, averaged 6.4 yards per attempt in rushing and 26.4 yards on kickoff returns.
Team captain at Army in 1929, he was featured on the September 23 cover of Time magazine of that same year. Cagle was noted for playing with the chin strap loose from his helmet, and sometimes without helmet. Sportswriters liked to refer to him as "Onward Christian" because of his ability to advance the ball.
He played professional football for five seasons. He was with the New York Giants from 1930 to 1932. In 1933, he and fellow former New York Giants player John Simms Kelly became co-owners of the NFL's Brooklyn Dodgers franchise. Cagle played for the team in 1933 and 1934. Dan Topping bought Cagle's half of the team in 1934.
Born in De Ridder, Louisiana, he was one of eight children, including five brothers and two sisters. Cagle was named after an uncle, who in turn was named after the late Bishop Christian Keener of the Methodist church. He attended high school in Merryville, a small community about 20 miles (30 km) southwest of De Ridder. According to local legend, he was known for getting off the school bus and racing it to school, a race that he quite often won. The football field at Merryville High School is named Keener Cagle Field in his honor.
Cagle was forced to resign before graduating from West Point for a violation of Army rules; He had secretly married Marian Haile after meeting her at Louisiana-Lafayette, and marriage was forbidden at the academy.
Cagle died in 1942, at 37 years of age, from a peculiar mishap the day after Christmas (December 26). He was discovered unconscious at the bottom of a Manhattansubway stairwell. According to The Advertiser report, "Cagle tripped and fell the full length of a flight of subway steps." He died three days later of a fractured skull. At the time of his death he had lived in a Queens apartment house with his wife and was employed by an insurance company.