Duff practiced law in Pittsburgh for thirty-six years, establishing the law firm of Duff, Scott and Smith. He also served as solicitor of Carnegie, and was an elector for Theodore Roosevelt in the 1912 presidential election. In addition to practicing law, Duff was engaged in the oil business for several years. He began by buying an oil driller's rig and taking a lease on some property about five miles from his home, where he struck oil. He subsequently engaged in ventures in other parts of western Pennsylvania as well as Mexico. He also served as president of the Criterion Oil Company and of the Westmoreland Natural Gas Company. He lost his fortune in the 1929 stock market crash, taking several years to recover financially. He was a delegate to the Republican National Convention in 1932, 1936, and 1940.