In 1915, Piron and Williams together started the Piron and Williams Publishing Company, and in their first year of business published Piron's composition, “I Wish That I Could Shimmy Like My Sister Kate”, which became his biggest hit. After touring briefly with W.C. Handy in 1917, he started an orchestra under his own name, which soon included such notables as Lorenzo Tio and Steve Lewis. Piron's New Orleans Orchestra quickly became the best paid African American band in New Orleans, for Piron landed regular jobs at both the Spanish Fort amusement park and the exclusive white New Orleans Country Club.
In 1923, Piron took his band to New York City as part of his ambition to make the group nationally known. He succeeded in making a hit there, landing a residency at the Roseland Ballroom, and making recordings for three different companies, Okeh, Victor and Columbia. The influence of Piron's band on the New York scene can be heard in the records of other New York bands of that time, such as Fletcher Henderson's (although Piron's influence on New York music would be eclipsed a year later when Louis Armstrong arrived in the city). In early 1924, some of Piron's band members were finding the cold northern winter and unfamiliar food and culture objectionable. Piron put the matter to a vote and, to Piron's frustration, the majority of the band voted to return home.
Back in New Orleans, he again lined up good jobs, returning to the Country Club, playing at Tranchina's Restaurant and on the excursion steamships Capital and President into the 1930s; in about 1935, he decided to dramatically change the sound of his orchestra to swing, in line with popular taste.