One of the terms of British Columbia entering into the Canadian Confederation in 1871 was the construction of a transcontinental railway connecting it with the original eastern Canadian provinces of Ontario, Quebec, New Brunswick, and Nova Scotia; this would result in a route through the largely-uncolonized Prairies, including the restive province of Manitoba, which had only recently been the site of the Red River Rebellion in 1869–70.

Under Fleming's direction, the symbolic "first spike" had been driven at Fort William (now part of Thunder Bay) in 1875, and construction had commenced with the goal of connecting Winnipeg with the Lake Superior Lakehead in Northwestern Ontario.

[8][9] The latter would pass through the newly formed Algoma District, paralleling the historic voyageur route through the North Channel of Lake Huron and connecting a number of pre-existing points or transportation corridors with the east: Additionally, by passing largely to the north of the La Cloche Mountains, which divide the interior from the Lake Huron shoreline, the railway's route would pass through fertile lands with agricultural potential that were noted as early as the 1847 and 1848 surveys by the Scottish geologist and explorer Alexander Murray.

Marie into the United States would benefit his St Paul, Minneapolis and Manitoba Railroad, and open up the possibility of a joint Canadian-American transcontinental mainline through the Midwest.

[9] It was also initially the more practical, as the CPR was being faced with the challenge of transporting construction materials to the Lakehead to complete the line through the Prairies.

[9][14] It was completed in 1884, but was considered below standard by the CPR, with bridges constructed from local timbers rather than the steel necessary to support heavy freight.

[9] This was intended to be the temporary western terminus of CPR line from Montreal, but construction on the eastern portion of the line north of Lake Nipissing had proceeded extremely slowly under engineer James Worthington, and only reached the Vermilion River by the end of 1883, in the process passing through a concentrated pocket of Jesuit missionary activity which would coalesce into the parish of Sainte-Anne-des-Pins.

[19] Ultimately, the line as it was built would later come under Canadian National ownership and most recently forms part of the CN Newmarket Subdivision.

[9] On 1 May 1884, Worthington also resigned from the company after a disagreement with Van Horne[20] and was replaced with Abbott as supervising engineer on the remaining eastern section of the mainline.

During blasting and excavation along the new mainline a short distance to the north of Sudbury, high concentrations of nickel-copper ore were discovered by Thomas Flanagan, a blacksmith working for the CPR, at the site of what would become the Murray Mine.

As well, in the course of charting his north–south meridian, Albert Salter observed "severe compass needle deflections" about 5 kilometres (3.1 mi) north of the Hudson's Bay Company trading post at Whitefish Lake.

Marie's industries, and the opportunity to open up the North Shore of Lake Huron to increased European settlement and natural resource extraction.

Much like in other areas of Canada, townships were quickly surveyed and lots sold either to natural resource interests or to prospective settlers, including Québécois, Scots, and Finns.

Marie, Sudbury, and Toronto; notably, in 1910 an express train derailed while crossing the Spanish River near the town of Nairn, resulting in scores of deaths and going on record as one of the worst railway disasters in Canadian history.

Marie-based Lake Superior Corporation, which served a more primarily industrial corridor largely north of the CPR line in the east, though it did operate some passenger services.

[8] During the Great Depression, a number of dairy farms in the area were permanently shut down and mining and lumber operations reduced to skeletons or mothballed entirely.

[11] This road was largely unusable in certain seasons, and for decades the only way to cross the Spanish River aside from the train bridge was a local ferry service run out of Nairn.

[14] This permanently shifted traffic away from communities near the CPR line like Turbine, High Falls, and Worthington, which quickly became ghost towns after experiencing a brief postwar economic revival due to the presence of the Soo Highway.

Additionally, due to the lack of a north-south CPR corridor paralleling the Algoma Central Railway (which had been built by the Lake Superior Corporation and was later acquired by the Canadian National Railway, or CN), the line was never used for through passenger services to Northwestern Ontario and Western Canada, as the CPR transcontinental mainline to the north was used instead.

With traffic declining, in 1997, Canadian Pacific leased the line to the Huron Central Railway, Inc., a subsidiary of Genesee & Wyoming.

[36] The railway had been asking the provincial government since 2006 for funding to improve track conditions, and in April 2009, Genesee & Wyoming warned that, due to the ever-deteriorating track and the resulting increased operational costs, it would be forced to shut down the railway, unless the provincial government would provide money with which to undertake the necessary upgrades.

Due to the economic downturn, it suffered a significant reduction in carload volume (down by almost 50% from the previous year) which rendered the line insolvent.

[41] Work began on August 10, 2011, with contracts going to Swift Contractors for tie replacement and track surfacing and M'Anishnabek Industries (a joint venture between B&M Metals of Sudbury and Serpent River First Nation) for ballast distribution.

[44][45] In early 2020, it was announced that G&W itself was being sold to Brookfield Infrastructure Partners and GIC Private Limited, the latter of which is the country of Singapore's sovereign wealth fund.

[46] Not long after this, in February, the closure of the Huron Central was officially postponed pending the possibility of further bailouts from the provincial and federal governments.

[49] It was announced on December 11, 2020, that due to ongoing negotiations with the Canadian federal government and the province of Ontario, that the deadline to close the line would be extended to June 30, 2021.

[55] The Transportation Safety Board of Canada released a report two years later on March 8, 2017, citing drainage issues and rail joint defects as the cause of the derailment.