Perrysville was platted and surveyed in 1825 by James Blair on a bluff on the west side of the Wabash River. The town is named for Commodore Oliver Hazard Perry, the hero of the Battle of Lake Erie. It became a local center for shipping products to New Orleans on flatboats via the Wabash, Ohio, and Mississippi Rivers, and it was also able to receive heavy equipment and manufactured items on steamboats.

 

Prior to the advent of the railroad in the second half of the nineteenth century, the town's location on the river made for a thriving community; it is reputed to have been the largest town between Chicago and Terre Haute at the height of its success. The arrival of the Wabash and Erie Canal enhanced its importance even further; a sidecut with locks allowed boats to be towed across the river to the town. Various roads intersected here, including a plank toll road from Danville, Illinois to the west, and stagecoach traffic became frequent. However, when the railroads did arrive, and failed to pass through the town, it spelled the eventual end of the vital river traffic, and of the importance of the town of Perrysville. 

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The Perrysville post office has been in operation since 1827.