Leitrim has a short length of Atlantic (Donegal Bay) coastline but is mostly inland country. Neighbouring Leitrim are the Ulster counties of Donegal to the north, Fermanagh to the northeast, and Cavan to the east, the Leinster county of Longford to the south and, to the west, the Connacht counties of Roscommon and Sligo. Fermanagh is in Northern Ireland while all the other neighbouring counties are within the republic. The River Shannon and Lough Allen divide Leitrim into North Leitrim and South Leitrim.

In ancient times, Leitrim formed the western half of the kingdom of Breifne. This region was long influenced by the O'Rourke family of Dromahair, whose heraldic lion occupies the official county crest to this day. Close ties initially existed with East Breifne, now County Cavan, and the O'Reilly clan seated there. The Normans invaded in the thirteenth century and occupied the south of Breifne until the exile of Irish landholders in 1620.

British Lord Deputy Sir John Perrot had ordered the legal establishment of "Leitrim County" a half-century prior, in 1565. Perrott also demarked the current county borders around 1583, enclosing the namesake grey mountains of the northwest and boggy glades of the southeast. Five forests are traditionally said to have stood in Leitrim up till the seventeenth century. Today's vast marshes likely formed soon after the county's trees were felled. Dampness quickly permeated the area's reputation: locals boasted that farmland "wasn't sold by the acre--it was sold by the gallon!". With such soil suitable solely for cows and potatoes, Leitrim's 155,000 residents (1841 census) were ravaged by the Potato Famine. After sixty years, the wounds had started to heal. William Butler Yeats spent the turn of the twentieth century fascinated with Lough Allen and the Sligo-march.