Meigs served in the local militia in Connecticut where he advanced to the rank of Captain. By 1775, he was appointed to the rank of Major in the 2nd Connecticut Regiment and then captured by the British & imprisoned at Quebec City in Canada. After a period of time he was released and returned to active duty as Major of the 3rd Connecticut Regiment. By February 1777, he was appointed Lieutenant Colonel of Sherburne's Additional Continental Regiment.

One of his most important achievements of the Revolutionary War was leading a raid against British forces in Sag Harbor, New York. With 220 men in a fleet of 13 whaleboats, he led the men to succeed in burning 12 ships and taking 90 prisoners without losing a single man. Afterwards, Congress awarded him a presentation sword for his heroism. Meigs received appointment as Colonel of the 6th Connecticut Regiment and served in that capacity until he was given command of the Corps of Light Infantry's 3rd Regiment. Colonel Meigs was retired January 1, 1781.

After the war, Meigs served as a surveyor of the Ohio Company before being appointed to fill the combined agent of the Cherokee Nation and military agent for the United States War Department. He first served at the Fort Southwest Point at Kingston but in 1807 was relocated to Hiwassee Garrison that was located near the mouth of the Hiwassee River where it joins the Tennessee River.

Meigs' role as a military agent ended in 1813 but he remained as Cherokee Agent until his death.

Meigs County, Tennessee is named for Colonel Return Jonathan Meigs.