The name O'Donnell comes from domnhaill, which means world mighty; it was a popular Irish personal name.

The main sept of the O'Donnells is associated with Tirconnell in Co. Donegal, and the family also has links with counties Clare and Galway. Red Hugh O'Donnell, the most famous of the clan, lived from about 1571 to 1602. He was the Earl of Tyrconnell and was closely involved with the ill-fated struggle against the English at the end of the 16th century, which resulted in the exile of the Irish chiefs (known as the Wild Geese). In Donegal town, the castle, now largely restored, was the O'Donnell stronghold.

One of the descendants of the Wild Geese was Leopoldo O'Donnell (1809-1867), a prime minister of Spain, and the Spanish connection remains important. The sole surviving member of the O'Donnells of Tirconnel is Father Aedh O Donel, born in 1940, a Franciscan missionary in Zimbabwe. The head of the clan will pass from him to Spanish cousins, the Dukes of Tetuan.