The European & North American Railway built a track up the Penobscot River valley from Bangor and reached Mattawamkeag in 1869.

By October 1871, the line was completed from Mattawamkeag to Vanceboro, where it connected through to Saint John, New Brunswick, Canada.

The parent company of the International Railway, Canadian Pacific, obtained running rights from Maine Central for Mattawamkeag to Vanceboro, where it regained CPR trackage in New Brunswick.

This placed Mattawamkeag on the transcontinental mainline of the Canadian Pacific, running from Saint John to Vancouver, British Columbia.

In 1974, CPR purchased the Mattawamkeag-Vanceboro railway tracks from Maine Central.

In 1988, CPR transferred trackage east of Megantic to its subsidiary Canadian Atlantic Railway.

In 1994, Canadian Atlantic was sold, with the line running through Mattawamkeag being purchased by J. D. Irving, and is now operated as the Eastern Maine Railway.

The George W. Smith Homestead (1874) in Mattawamkeag is listed on the National Register of Historic Places.