The 3rd South Carolina participated in the First Siege of Charleston in 1775–1776, and became part of the 1st South Carolina Brigade on 23 November. It fought in engagements in the Piedmont and transferred to the 2nd South Carolina Brigade on 26 August 1778. Detachments of the regiment served in the Cherokee War of 1776 and in the expeditions to Florida during 1777 and 1778. The 3rd South Carolina was relieved from the latter on 3 January 1779 and became part of the South Carolina Brigade on 1 February.