Witherspoon was born in Gurdon, Arkansas. He first attracted attention singing in Calcutta, India, with Teddy Weatherford's band, which made regular radio broadcasts over the U.S. Armed Forces Radio Service during World War II. Witherspoon made his first records with Jay McShann's band in 1945. He first recorded under his own name in 1947, and two years later with the McShann band, he had his first hit, "Ain't Nobody's Business," a song that came to be regarded as his signature tune. In 1950 he had hits with two more songs closely identified with him—"No Rollin' Blues" and "Big Fine Girl"—and also with "Failing by Degrees" and "New Orleans Woman", recorded with the Gene Gilbeaux Orchestra (which included Herman Washington and Don Hill) for Modern Records. These were recorded at a live performance on May 10, 1949, at a "Just Jazz" concert in Pasadena, California, sponsored by Gene Norman. Another classic Witherspoon composition is "Times Gettin' Tougher Than Tough".