The area that is now Main Township was part of Augusta Township, then Catawissa Township until 1799, and part of Mifflin Township until January 1844. The Pennsylvania Railroad once passed through the township. In 1808, the Reading Road was created and passed through Main Township, allowing easier access to it. By this time, several settlers had arrived and settled in the township.

Main Township was settled by settlers of European descent in 1772, at which time the township was part of Berks County.

The main historical industry in Main Township was the iron industry. In 1815, a charcoal-iron furnace was built in the township.

Fisher Run Road looking north in Main Township

Main Township is located just south of the center of Columbia County and is bordered to the north by the Susquehanna River, lined by 500-foot-high (150 m) bluffs. The unincorporated community of Mainville is in the center of the township. The ridges of Nescopeck Mountain and Catawissa Mountain cross the township just south of Mainville, separated by a water gap formed by Catawissa Creek.