After graduation, he was appointed an Indian agent in 1811. During the War of 1812, he served as adjutant of a Cherokee regiment under the command of Andrew Jackson. After the Red Stick War ended, Ross demonstrated his business acumen by starting a tobacco plantation in Tennessee. In 1816, he built a warehouse and trading post on the Tennessee River north of the mouth of Chattanooga Creek, and started a ferry service that carried passengers from the south side of the river (Cherokee Nation) to the north side (USA). His businesses served as the start of a community known as Ross's Landing on the Tennessee River (now Chattanooga, Tennessee). Concurrently, Ross developed a keen interest in Cherokee politics and attracted the attention of the Cherokee elders, especially Principal Chiefs Pathkiller and Charles R. Hicks, who, along with Major Ridge, became his political mentors.