Columba was born in December 521 A.D. into a noble family in County Donegal, Ireland. On his father's side he was great-great-grandson of Niall of the Nine Hostages, an Irish high king of the 5th century.

In early Christian Ireland the druidic tradition collapsed due to the spread of the new Christian faith. The study of Latin learning and Christian theology in monasteries flourished. Columba became a pupil at the monastic school at Clonard Abbey, situated on the River Boyne in modern County Meath.

Tradition asserts that, sometime around 560, he became involved in a quarrel with Saint Finnian of Moville over a psalter. Columba copied the manuscript at the scriptorium under Saint Finnian, intending to keep the copy. Saint Finnian disputed his right to keep the copy. The dispute eventually led to the pitched Battle of Cúl Dreimhne in 561, during which many men were killed. A synod of clerics and scholars threatened to excommunicate him for these deaths, but St. Brendan of Birr spoke on his behalf with the result that he was allowed to go into exile instead. Columba suggested that he would work as a missionary in Scotland to help convert as many people as had been killed in the battle. He exiled himself from Ireland, to return only once again, several years later.

In 563 he travelled to Scotland with twelve companions, where according to his legend he first landed at the southern tip of the Kintyre peninsula, near Southend. However, being still in sight of his native land he moved further north up the west coast of Scotland. In 563 he was granted land on the island of Iona off the west coast of Scotland which became the centre of his evangelising mission to the Picts. However, there is a sense in which he was not leaving his native people, as the Irish Gaels had been colonizing the west coast of Scotland for the previous couple of centuries. Aside from the services he provided guiding the only centre of literacy in the region, his reputation as a holy man led to his role as a diplomat among the tribes; there are also many stories of miracles which he performed during his work to convert the Picts. He visited the pagan king Bridei, king of Fortriu, at his base in Inverness, winning the king's respect, although not his conversion. He subsequently played a major role in the politics of the country. He was also very energetic in his evangelical work, and, in addition to founding several churches in the Hebrides, he worked to turn his monastery at Iona into a school for missionaries. He was a renowned man of letters, having written several hymns and being credited with having transcribed 300 books. One of the few, if not the only, times he left Scotland after his arrival was toward the end of his life, when he returned to Ireland to found the monastery at Durrow.

Columba died at Iona on 9 June 597 A.D. and was buried by his monks in the abbey he created. He was later disinterred and is reputed to be buried in Downpatrick, County Down, with St. Patrick and St. Brigid or at Saul Church neighbouring Downpatrick.

Several islands are named after Columba in Scotland, including Ì Chaluim Chille (one of the Scottish Gaelic names of Iona), Inchcolm and Eilean Chaluim Chille.