[3] The city has three Canada–US border crossings (also known as ports of entry) over the St. Croix River connecting to St. Stephen, New Brunswick, Canada.

The historic Passamaquoddy, an Algonquian-speaking people of the Wabanaki Confederacy, was predominant in this area at the time of European encounter and settlement.

The first permanent settler was Daniel Hill of Jonesboro, who arrived in 1779 during the American Revolutionary War, when this was still part of Massachusetts.

On June 27, 1789, the Massachusetts General Court sold the township to Waterman Thomas for 19¢ an acre (0.4 hectares) (approx.

[5] The relationship between Calais and the neighboring Canadian town of St. Stephen has been remarkably close, over a period of many years.

As evidence of the longtime friendship between the towns a likely apocryphal[6] story is told that during the War of 1812, the British military provided St. Stephen with a large supply of gunpowder for protection against the enemy Americans in Calais, but St. Stephen's town elders gave the gunpowder to Calais for its Fourth of July celebrations.

[8] It was built to transport lumber from a mill on the St. Croix River opposite Milltown, New Brunswick, 2 miles (3 km) to the tidewater at Calais in 1835.

On July 18, 1864, Confederate agents crossed the border from New Brunswick and attempted to rob a bank in Calais.

Significant features on the property include a 340-foot (100 m) high granite headland towering over the estuary, a low-tide sand and boulder beach, upland forest, and abundant wildlife.

Some past city managers include: William Bridgeo, Nancy Orr, Nicholas Mull, Linda Pagels, Mark Ryckman, Diane Barnes and James Porter.

Calais is located at the junction of U.S. 1, a major north-south highway that runs along the Eastern Seaboard, and Route 9, which crosses the state from east to west.

Since October 25, 2012, the city also has had direct access to New Brunswick Route 1, a controlled-access freeway that begins at the Canada–US border and runs east through Saint John to a junction with the Trans-Canada Highway.

It serves northeastern Washington County with an approximate population of 14,000 from Topsfield to the north, Wesley to the west, and Eastport to the south.

[18] The new inspection facility alleviates traffic congestion from downtown Calais and the neighboring towns in Canada.