Loyalists, mostly Scottish Highlanders, many of whom did not have muskets and were wielding broadswords, expected to find only a small Patriot force on February 27, 1776. Before the arrival of the Loyalists, the Patriots removed the planks from the bridge that crossed Moore's Creek. After removing the planks of wood, they smeared the remaining crossing beams with lard. This forced the Loyalists to cross the bridge in single file. As the Loyalists advanced across the bridge, Patriot shots rang out and dozens of Loyalists fell into the creek below, including their commanders. At the time, the creek was an estimated six feet deep. One commander, Lieutenant Colonel Donald McLeod, died in the battle. Another commander was Colonel Allan MacDonald, the husband of Flora MacDonald of Highland lore who aided Bonnie Prince Charlie following the Jacobite defeat at Culloden Moor in 1746.

Stunned, outgunned and leaderless, the Loyalists either surrendered or retreated in confusion. Wagons, weapons and British Pound sterling worth more than $1 million by today's value were seized by the Patriots in the days following the battle.

This dramatic victory ended British authority in the colony and greatly influenced North Carolina to be the first colony to vote for independence. The Battle of Moores Creek Bridge, coupled with the Battle of Sullivan's Island near Charleston, South Carolina, a few months later, were the first open conflicts of the American Revolution. Both ultimately led the Thirteen Colonies to declare independence on July 4, 1776.