Winchester Repeating Arms Company introduced the rifle and cartridge at the United States Centennial Exposition.

The cartridge and rifle enjoyed brief popularity with Gilded Age American hunters including Theodore Roosevelt, and was issued to the Canadian North-West Mounted Police and to Texas Rangers.

[4] Nomenclature of the era indicated the .45-75 cartridge contained a 0.45-inch (11.43 mm) diameter bullet with 75 grains (4.9 g) of gunpowder.

Although the .45-75 was nominally superior to the popular .45-70, the weak toggle-link action with its elevator-style carrier originally designed for handgun cartridges limited the ability of the Model 1876 rifle to safely fire higher pressure loads intended for stronger actions.

Within a decade, the Model 1876's advantage of faster loading for subsequent shots was eclipsed by the stronger and smoother Winchester Model 1886 action capable of handling longer cartridges, including the .45-70 with varying lengths for 300 and 500 grain bullets.