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The Mohawk and Malone Railway crossed the northern Adirondacks at Tupper Lake Junction, just north of Tupper Lake.

In 1890, the New York Central did not control any rail lines north of the Mohawk Valley, and no railroad crossed the Adirondacks. Rome, Watertown and Ogdensburg Railroad and the Utica and Black River Railroad each ran north to Ogdensburg well west of the Adirondacks, where they connected with the Ogdensburg and Lake Champlain Railroad. The Delaware and Hudson ran north up the Champlain Valley to the east of the Adirondacks by 1876, connecting with the Grand Trunk Railway to Montreal, and the Adirondack Railway ran north from Saratoga to North Creek by 1870.

Dr. William Seward Webb was president of the Wagner Palace Car Company. He began by purchasing the narrow gauge Herkimer, Newport and Poland Railroad, completed in 1881, that ran 16 miles north from Herkimer to Poland. Webb converted its trackage to standard gauge and straightened it to avoid multiple crossings of the West Canada Creek. He then had track built from Tupper Lake to Moira and thence to Montreal. This was called variously the Adirondack and St. Lawrence Railroad and the Mohawk and Malone.

After 1893, it was controlled by the New York Central and Hudson River Railroad.

It opened in 1892 from Malone Junction to Childwold Station with a branch from Lake Clear Junction to Saranac Lake. In 1913, it merged with the New York Central and Hudson River Railroad as the "Adirondack Division".