When it was built, Hadrian’s Wall represented the far northern edge of the colossal Roman Empire. Tullie House has the largest collection of finds from the western end of the Hadrian’s Wall. The frontier was first established along the line that was called the Stanegate (stone street) in Medieval times. This ran from Carlisle to Corbridge. Recent excavations have shown that the fort at Carlisle, which lay between the castle and Tullie House, was occupied from AD 72/3 to the early fifth century. It predated the Stanegate frontier, but was incorporated into it around AD 103-5.

In AD 122, Hadrian ordered the wall that bears his name to be built. The wall ran north of Carlisle through Uxelodunum (modern Stanwix, now a suburb of Carlisle). This was the largest fort on Hadrian's Wall, but is now buried under the later settlement. Tullie House has artefacts collected from the western half of the Hadrian’s Wall, complimenting the collection in Newcastle from the eastern half. The sites represented include Birdoswald, Castlesteads, and Bowness-on-Solway. Archives from excavations undertaken by Sir Ian Richmond and F G Simpson, among others, are housed in the museum.