He was appointed to the post of brigadier general of the "Salisbury District Brigade" in May 1776, and he participated in the initial phases of the wars against the Cherokee Indians along the frontier.

He was listed as a member of the North Carolina General Assembly in 1766, a sheriff and justice of the peace of Rowan County from 1767 to 1769, and a tax collector.

[11] Rutherford entered the war in 1775 as a colonel in the North Carolina militia after his appointment to the Rowan County Committee of Safety.

[13] Rutherford represented Rowan County at the Fourth Provincial Congress in Halifax, from April 4 to May 14, 1776, during which he helped develop and write the North Carolina Constitution and was promoted to brigadier general of the Salisbury District Brigade.

[3][14] In the summer after the conference, he raised an army of 2,400 men to campaign against local Cherokee Indians,[14] who had been attacking colonists on the western frontier since their alliance with the British.

[14] From there, the three groups traveled through the Blue Ridge Mountains at the Swannanoa Gap, passed up the valley of Hominy Creek, and crossed the Pigeon River.

They then passed through Richland Creek, near the present-day town of Waynesville, North Carolina, and crossed the Tuckasegee River near an Indian settlement.

After that conflict, they marched to the Overhill Cherokee "Middle Towns" (on the Tennessee River), where he met General Andrew Williamson of South Carolina on September 14[15] at Hiwassee.

[15] The now-four regiments skirmished with hostile Indians at Valley Town, Ellijay, and near the southern Watauga settlements (present day northeast Tennessee).

Rutherford moved his troops near Augusta, where he supported General John Ashe during the Battle of Brier Creek on March 3.

[23] The loss of Charleston in 1780 was a huge blow to the Patriot cause and posed a significant threat to neighboring North Carolina, which lacked adequate defenses due to expiring enlistments.

[24][25] After rallying troops at Charlotte, Rutherford received information that Loyalists were gathering at arms at Ramsour's Mill, near present-day Lincolnton, North Carolina, and issued orders for local officers to disperse the group before they evolved into an even greater threat.

After collecting troops from Rowan and Mecklenburg Counties, Rutherford moved his men to the Catawba River and crossed it at the Tuckasegee Ford on June 19.

He sent word to Colonel Francis Locke of Rowan County, to rendezvous with him about 16 miles (26 km) from Ramsour's Mill, near the forks of the Catawba.

[26] The losses at Savannah, Charleston, and the Wexhams had practically driven the Continental Army from the South, with state defenses reduced to a number of locally led partisan militias.

In response to the loss of military presence, Congress sent Horatio Gates, who had distinguished himself at Saratoga, to reform the Continental Army in Charlotte, North Carolina.

[27] Against the advice of his officers and without knowing the capabilities of his troops, some of whom were untested in battle, Gates marched toward South Carolina on July 27 with over 4,000 men.

[30] After a short reunion with his family, Rutherford trained and took command of 1,400 men of the Salisbury District Brigade and allegedly began to attack Tory militias and communities brutally, according to several reports sent to his superior, General Greene.

[33] In October and November, Rutherford continued to force the Loyalists into Wilmington, eventually surrounded the city, and successfully cut off British communications and supply lines.

The commanding British officer, Major Craig, was soon informed of Cornwallis's surrender at Yorktown, and his forces at Wilmington were hastily evacuated.