Rev Calum MacLeod, 46, was voted in by the St Giles' congregation in Edinburgh on Sunday and will move from the Fourth Presbyterian Church in Chicago after being there for 16 years.
He replaces Very Rev Dr Gilleasbuig Macmillan.
The 14th Century cathedral, of the Royal Mile, is currently at the centre of a row after a move to carve the building's name above the front entrance.
Mr MacLeod, who will take up his first post as a minister in Scotland, said he was "humbled and honoured" to be selected.
He said: "This historic and important church in the heart of Edinburgh has, I believe, a vital role to play in the life of the city and the nation at this critical time for our country and on into the future.
"It is an exciting time to return, with my wife, Missy, to my homeland."
Born in Glasgow, Mr MacLeod was educated in the city of his birth where he obtained a BA in economics in 1989 from Strathclyde University and a BD from Glasgow University in 1994.
His appointment comes as the row over carving the title of the cathedral into the building is debated.
The Kirk Session is moving to carve into stonework above the main door.