Probably the oldest of the MacEwen clans is descended from a branch of the Bissets (a Scottish family of Norman origin), which settled in Antrim, Ulster, and took the name of MacEwen from their chief John (Eoin) Bissett in the thirteenth century - in Ireland they are most often known as McKeowns. Like their neighbours, the Agnews of Larne, the MacEoin Bissets joined the invading Scots under Edward Bruce and his son Alexander. When Alexander Bruce gained the Lordship of Galloway, he apparently granted the castles of Wigtown and Lochnaw to his MacEoin and Agnew allies. Patrick MacEwyn [MacEoin] is recorded as provost of the castle at Wigtown in 1331. In the late fourteenth century, when the great grandson of the first Lord Agnew of Galloway was beset in Lochnaw Castle by Black Archibald Douglas, it was the MacEwens who came to the rescue.

Clan Ewen of Otter probably takes its name from the fourteenth-century chief listed as Eogain in the medieval genealogy of the clan (MS 1467). This Ewen of Otter was descended from the early-medieval prince Anrothan, and through him from Niall of the Nine Hostages and the High Kings of Ireland. Their clan lands were in Cowal on the shores of Loch Fyne, where they were surrounded by the kindred clans of MacLachlan and Lamont. This clan was dispossessed at the death of the fourth chief Swene in 1493, when the core of the clan seems to have moved to the lands of Lennox on the shores of Loch Lomond.

In the sixteenth century, the adherents of Donald MacEwen Cameron were also styled Clan Ewen and probably took the surname MacEwen. Donald MacEwen was the son of Ewen, 14th chief of Clan Cameron, born out of wedlock to a daughter of the MacDougall chief. He gained fame through his prowess as a warrior and his loyalty to the clan Cameron, earning himself the nickname Taillear Dubh na Tuaighe (The Black Tailor of the Axe) when he slew the Mackintosh of Mackintosh at the Battle of Bun Garbhain (Bun Garvan, c.1570). He also led raids against the MacGregors on behalf of Grey Colin Campbell of Glenorchy. All the records of this clan are concentrated in the western Highlands and islands.

Another branch of Clan Cameron might also have descendants named MacEwen. Camerons of the line of Ewen MacEwen Cameron of Erracht, Sliochd Eòghainn Mhic Eòghainn, were certainly known by the name MacEwen in the sixteenth century.

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