Radiocarbon dating of a nearby dig site indicated Clayton was once home to a 2-3 long house, 180 person palisade ringed habitation, circa 1470.

The arrival of the railroad in 1873 marked a major turning point in the local tourist industry.

Simon Johnston House are listed on the National Register of Historic Places.

Clayton is accessible by automobile via New York State Route 12, which turns east from its northward course in the village.

Beginning in 1873, the village was served by the Clayton Division of the Rome, Watertown and Ogdensburg Railroad (RW&O), which later became a part of the New York Central network.

At its peak, multiple express trains per day ran from Niagara Falls and Grand Central Terminal to bring passengers and freight to Clayton's ferry terminal, which was the gateway to the Thousand Islands region.

The New York Central passenger trains included direct sleeping car service.

The station and ferry terminal were converted into Frink Park, a public venue for performances and mooring for visiting ships, while the rail yards were incorporated into the property of the Frink-America snowplow factory, which was demolished in 2010.

The remainder of the right-of-way within the village is maintained as the Sissy Danforth Rivergate Trail, a multi-use recreational trail maintained by the Thousand Islands Land Trust and the Rivergate Wheelers ATV club.