The portion of US 40 Alternate between Frederick and Boonsboro roughly follows the Monocacy Road, a pack-horse trail blazed by settlers from Pennsylvania around 1730. The trail connected Philadelphia, Lancaster, and Hanover with Winchester, Virginia by way of what is now Taneytown, Frederick, Boonsboro, and Williamsport. The portion of the Monocacy Road from Frederick to Williamsport was used by the Braddock Expedition on its way from Alexandria to Cumberland to commence its ill-fated assault on Fort Duquesne. Following the founding of Hagerstown in 1762, a road was laid out north from Boonsboro to connect the new town with the eastern part of the colony. While the Monocacy Road as a whole was disused by 1794, the portion followed by US 40 Alternate remained an important connection between Baltimore and Western Maryland.