The Harrisburg, Portsmouth, Mountjoy & Lancaster Rail-Road (HPMtJ&L) was an early American railroad built to connect three main population centers in east-central Pennsylvania.

In 1834, the Commonwealth of Pennsylvania chartered the Portsmouth and Lancaster Rail-Road, one of the earliest in the United States being organized only six years after the first, the Baltimore and Ohio Railroad.

[2]: 3 The HPMtJ&L followed the east side of the Susquehanna River, surveyed and located in 1834 to connect the Susquehanna River valley communities of Harris Ferry (now Harrisburg), Portsmouth (now a part of Middletown), Mount Joy, and Lancaster, Pennsylvania.

Construction work began in 1835 and the main line completed in 1838, concluding with a tunnel built just outside of Elizabethtown.

This lease brought the last piece of railroad between Pittsburgh and Philadelphia under the control of the PRR.