The town is located near an exit for Interstate 95, on the north side of the outlet of the Susquehanna River.

Perryville was first settled by Europeans in 1622, when Edward Palmer was granted a patent for a settlement on what is now Garrett Island.

During the 17th century, Lord Baltimore granted George Talbot 31,000 acres (130 km2) of land, which included the Perryville area.

Colonel John Rodgers (1728–1791), who operated the ferry and tavern in Perryville, raised the 5th Company of the Maryland Militia.

This company became part of the famous Flying Camp and was instrumental during the early stages of the Revolutionary War.

To transport troops and munitions to Annapolis, the Union Army again began the operation of the ferry across the Susquehanna.

[3] During the 20th century, it was an important destination for those going to the United States Naval Training Center Bainbridge, Maryland, about three miles up the road, now no longer functioning and sold by the Navy.

Perryville is currently home to the Perry Point Veteran's Medical Center, located on a picturesque campus at the outlet of the Susquehanna River into Chesapeake Bay.

This same location is also the Northeast Campus of AmeriCorps National Civilian Community Corps, a residential national service program which recruits young Americans between the ages of 18 and 24 to perform community service in various locations in the country.

Perryville is the northern terminus of the MARC Penn Line commuter rail service, which runs south to Washington, D.C. via Baltimore.

Perryville is home to the largest linwood tree in Maryland, located at 50 Millcreek Road on an estate known formerly as the Anchorage.

[9] The distribution center’s total 4.9-MW solar installation of 25,913 panels generates 6,092,533 kWh of clean electricity yearly.

The revenues from the casino are divided with the Town of Perryville and Cecil County government as well as the state.

Interstate 95 crosses the north edge of town, with an interchange at Maryland Route 222 providing direct access.

Cecil Transit provides bus service to Perryville along the Route 2 Cross-County Connection to North East and Elkton.