He was the man upon whom the book My Philadelphia Father and the play and film The Happiest Millionaire were based. He trained men in hand-to-hand combat in both World War I and World War II, was a fellow of the American Geographical Society and founded a movement called "Athletic Christianity" that eventually attracted 300,000 members around the world. A 1955 Sports Illustrated article called him "boxing's greatest amateur" as well as a "major factor in the re-establishment of boxing as a legal and, at that time, estimable sport."

He was born on October 1, 1874, in Philadelphia, Pennsylvania, to Edward Biddle II and Emily Drexel. He was a grandson of banker Anthony Joseph Drexel, and a great-grandson of banker Nicholas Biddle. Biddle was a graduate of Germany's Heidelberg University.

An officer in the United States Marine Corps, Biddle was an expert in close-quarters fighting and the author of Do or Die: A Supplementary Manual on Individual Combat, a book on combat methods, including knives and empty-hand skills, training both the United States Marine Corps in two world wars and special agents of the Federal Bureau of Investigation. He can be seen training Marines in the RKO short documentary Soldiers of the Sea. He was considered not just an expert in fighting, but also a pioneer of United States Marine Corps training in the bayonet and hand-to-hand combat. He based his style on fencing, though this approach was sometimes criticized as being unrealistic for military combat.

Having joined the Marines in 1917 at the age of 41, he also convinced his superiors to include boxing in Marine Corps recruit training. In 1919, he was promoted to the rank of major, and became a lieutenant colonel in 1934. In Lansdowne, Pennsylvania, right outside of Philadelphia, Biddle opened a military training facility, where he trained 4,000 men. His training included long hours of calisthenics and gymnastics, and taught skills such as machete, saber, dagger, and bayonet combat, as well as hand grenade use, boxing, wrestling, savate and jiujitsu. He also served two years in the National Guard.

A keen boxer, Biddle sparred with Jack Johnson and taught boxing to Gene Tunney. He even hosted "boxing teas" in his home, where other boxers would spar a couple of rounds with him and then join the family for dinner. A February 1909 match with Philadelphia Jack O'Brien was attended by society leaders including women in elegant evening gowns.

He served as a judge in the fight between Jack Dempsey and Jess Willard on 4 July 1919.

On February 5, 1920, Biddle, as chairman of the Army Navy and Civilian Board of Boxing Control of New York, became a member the International Boxing Union.

During World War II, Biddle returned to active duty with the Marine Corps with the rank of colonel and taught hand to hand combat to recruits.