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Two Cree women with snowshoes photographed at the Morrison (later Shekak) River settlement in 1928.
First Nations people have lived in the area for centuries, as indicated by archaeological evidence such as potsherd fragments. These are concentrated in the areas around Lake Nagagamisis, which is 30 kilometres (19 mi) to the north of Hornepayne, as well as the Shekak River to the west, rather than near Hornepayne itself, which before the arrival of the railway was largely remote and uninhabited.: 87  In the 19th century, they became involved in the fur trade and the mercantile activities of the Hudson's Bay Company. By the early 1900s, they consisted of three Cree families living at Lake Nagagamisis, along with a number of Ojibwe who were possibly originally from Heron Bay.: 87  With the opening of the railway, they abandoned their existing trading post on Lake Nagagamisis in 1926 for a new settlement on Shekak Lake, which was closer to the rail line.: 87  By the 1940s, many of them had moved to Hornepayne to work in the railway and timber industries based in the town. A number of their descendants are members of the Hornepayne First Nation, a member organization of the Nishnawbe Aski Nation.
Hornepayne differs from a number of older Northern Ontario settlements due to its distance from major waterways, making it relatively inaccessible before the advent of rail transportation in the north.: 87  The townsite was originally surveyed in 1877, when possible routes for the Canadian Pacific Railway transcontinental mainline were being explored.: 87  Instead of Canadian Pacific, however, Hornepayne would become associated with the Canadian Northern Railway (CNoR), one of several railways which were later amalgamated into the Canadian National Railways (CN) system during the 20th century. The Canadian Northern built its line through the area in 1915 and established a divisional point on the line called Fitzback. In 1919, the Canadian Northern was amalgamated into the Canadian National system. A year later, in 1920, the point was renamed Hornepayne, after the railway financier Robert Montgomery Horne-Payne.: 87 
In the steam era, the railway system was labour-intensive and required many workers for maintenance of way, crew changes, and to resupply trains with coal and water at fixed intervals. This circumstance fostered the growth of "railway towns", as railway workers began to create permanent settlements to live in with their families. Sections of track were broken up into subdivisions, which were approximately 200 kilometres (120 mi) long and were separated by divisional points. Divisional points acted as a sort of local "headquarters" for the railways, and were very important for their operations. Additionally, most steam trains needed to be resupplied with coal at least once and water at least three times when passing through each subdivision, requiring railways to maintain even more permanent or semi-permanent settlements to support these operations. Hornepayne, as a divisional point, sat at the joining place between the CN Oba Subdivision (east to Foleyet) and the CN Caramat Subdivision (west to Nakina).: 78 
Hornepayne initially had few permanent structures aside from the railway station, but was inhabited mostly by railway workers, who were young and well-paid for the era. A one-room schoolhouse was constructed in 1921 at the corner of First and Front streets, partially replacing the railway coach which was previously used as a school, though senior students were shifted to the old railway station. A new railway station, which was demolished in 2020, was also constructed in 1921. The situation was resolved when town ratepayers authorized $30,000 be spent on the construction of a new four-room school in the winter of 1923.: 88 
Throughout the 1920s, Hornepayne grew, and soon was home to several grocery and general stores, as well as a butcher shop, a dress shop, a pharmacy, a Hudson's Bay Company store, two barbershops, a town hall, two restaurants, a bowling alley, two pool halls, and two hotels, one of which was owned by CN and one of which was independent.: 88  The town lacked in fresh fruit and vegetables early on, which were imported by rail from Port Arthur. Later, two farms, one of which was a dairy farm, were established in the area to feed the town. By the 1930s, one farm had around four hundred chickens.: 89  Due to its remote location, household electricity was slow to arrive in Hornepayne. Diesel-generated power was available from CN for most of the town starting in the 1930s, but the town would only be connected with the Ontario electrical grid in 1962.: 89 
Highway 631 as seen in 2009.
The town was incorporated in 1927–28 by local petition, and was poised to become a regional centre. A series of devastating fires in 1929–31, however, destroyed many of the town's commercial buildings, as well as the CNR shops. Rail traffic slowed during the Great Depression, and the town struggled, with some residents finding employment on highway construction under government public works funding.: 90  This difficult and slow work culminated in the opening of the northern section of Highway 631 in 1959, linking Hornepayne with Highway 11. In 1973, the highway was extended to the south to connect to Highway 17 at White River.: 91 
The Hallmark Centre was a mixed-use development in the town, which opened in 1982 and closed in 2011.
In the 1970s and 1980s, Hornepayne underwent a considerable redevelopment push, spurring the southern highway extension, the opening of the Hornepayne Municipal Airport, and the creation of the mixed use Hallmark Centre "mall", merging together a number of commercial, recreational, and institutional aspects of the town. At various times, it included residences for CN temporary workers (an evolution of the CN bunkhouses which were demolished in the 1950s), a post office, the local high school, a hotel, a library, a swimming pool, a gym, apartments, and a Hudson's Bay Company Northern Store department store. Many existing businesses relocated to the complex, though some remained at their old locations.: 92  Over the years, the complex became less and less commercially viable, and closed entirely in 2010.
