Though the town expanded considerably throughout the nineteenth century, it did not escape the effects of famine and disease.
In 1818 the area suffered a fierce outbreak of typhus fever. A wander around the local graveyards gives some idea of the number who died as a result. Several of the local ministers lost their lives in this epidemic and their names are recorded on the memorial plaques of the local churches. One such is David McAnally, surgeon of the Armagh Militia. During the outbreak, he treated many of the inhabitants of the locality and saved over two hundred lives before succumbing to the disease himself.
Famine in Ireland in 1846-49 was the result of reliance on the potato crop as a source of food and income. When the potato blight struck, thousands of people lost their lives as the result of starvation and still more left the island of Ireland to seek a better life elsewhere. The inhabitants of Markethill and District were not as badly affected by the potato famine as were the towns and villages in the south and west of Ireland. The citizens of the locality had long since diversified and were not so dependent upon the potato crop as other people in Ireland. The area did suffer depleted food resources at the time and Sir Archibald Acheson set up a soup kitchen for their relief. Fever broke out and a fever hospital was established in the town of Markethill to help care for the sick.
Despite the Great Famine, the population of Markethill fell by only 55 between the years of 1841 (pre-famine) and 1851 (post-famine). It was in the decades following that the population fell more significantly, possibly more to do with emigration.