[4][5] Following the fall of Fort Sumter in mid-April 1861, during the opening months of the American Civil War, the Hanover Junction Railroad Station became a key transportation hub for the movement of Union Army soldiers from the Commonwealth of Pennsylvania to Maryland, Washington, D.C. and other areas in the southern United States where federal troops were stationed to protect cities, towns, and critical infrastructure points endangered by Confederate States Army incursions.

[6] Train traffic through Hanover Junction then continued to grow as horses and supplies were added to the increasing number of Union soldiers being transported as the war turned into a multi-year conflict.

On June 27, Confederate troops led by Jubal Early occupied the town of Carlisle, and then advanced toward Hanover Junction, which had been able to maintain telegraph communications with state and military leaders in Harrisburg.

Following the Union Army's victory, which helped turn the tide of war in favor of the federal government, Hanover Junction became a critical hub for transporting thousands of wounded soldiers from the battlefield aide stations where they had received immediate lifesaving care to federal military hospitals in Baltimore, Harrisburg, York, and other northern towns, which had significantly better access to advanced medical treatment options for the severe traumatic injuries that many of the soldiers had received.

It is also a restroom stop for the York County Heritage Rail Trail, a bicycle and walking path which parallels the old tracks of the Northern Central Railway.