The city of Mosinee was originally known as Little Bull Falls and probably named from the roaring falls and rocky river passage on which it was situated.

The community's origins are usually traced back to the establishment of its first major business - a sawmill- opened by John L. Moore in 1836. Through the course of the following two decades, the mill changed hands, eventually ending up under the capable sole ownership of Joseph Dessert. In the mid 1800's, lumbering was the major industry in central Wisconsin and highly profitable. Estimates report that, during this period, each year over 125 million feet of manufactured lumber was produced by 20 area sawmills and floated down the Wisconsin River by the efforts of some 2,500 strong men to be marketed in the "lower" country. The floating of large rafts made up of logs and or lumber down the Wisconsin River was a common site and a frequently dangerous occupation. Stories abound of the mishaps and miracles of such log "cribs" shooting the dangerous rapids known as Little Bull Falls, but the overall rate of success was high and business was prosperous.

Soon after the establishment of the sawmill, supporting businesses sprang up. A boarding house, grocery store, saloon, tannery, gristmill, and blacksmith shop were all opened. Yet, for many years, transportation to the area remained a significant difficulty. Due to the community's initial growth primarily on the western side of the Wisconsin River, the building and maintenance of bridges connecting Mosinee to the eastern side of the river was of vital importance. From the completion of the first bridge over the falls in 1856, time has seen their evolution from sturdy wooden structures through heavy ironwork to their current concrete lanes.