Born in Ireland, Murphy came to St. Louis at the age of 13 to work on his grandfather´s 300-acre farm near Creve Coeur Lake. By the time he reached St. Louis, the farm had been foreclosed upon. By 1820 he became an apprentice to Daniel Caster, a St. Louis wagonmaker. He was very talented at making wagons, and eventually opened his own shop on a spacious lot on Broadway, between Cass and O´Fallon.

Most wagons at that time carried about one thousand pounds of merchandise, but Murphy´s teamster wagons, drawn by four oxen, were capable of carrying close to five thousand pounds of merchandise. This was important for two reasons. First, the large oxen scared off the Indians. Second, the governor of Santa Fe had put a tax on wagons, regardless of size. Murphy’s large load wagons kept many traders from going bankrupt, since they did not have to pay any more tax than a small wagon.

Murphy´s business grew into a million-dollar company. By the time he retired at the age of eighty, he had built more than two hundred thousand wagons.