The town of Pittsboro was founded on December 9, 1834, by Simon T. Hadley and Wiliam L. Matlock. The town was named "Pittsborough" in honor of Hadley's home in North Carolina. The spelling was later changed to "Pittsboro".
On April 6, 1906 an election was held for incorporation of the town. The result of the election was 83 favorable and 38 opposed. After incorporation came many infrastructure improvements and new services. Sidewalks were laid, street lights installed, and water service begun.
In 2008 Pittsboro had a parade for olympic silver medalist, Bridget Sloan. It led down to the high school (in neighboring Lizton, Indiana) where she thanked her fans for supporting her. Hundreds of people had lined main street with signs and banners.
In 2009 Pittsboro celebrated its 175th birthday. The celebration was from June 26 through the 28. The celebration included a temporary museum of the town's history and signs on the buildings that say "On this site" and tells you the history of the building and what was here before. The celebration also included food, activities, music, a parade, and fireworks.