It was built as a smart tree-lined avenue in late Victorian times and improved over the next half century as a local shopping place for its neighbourhood and the affluent area to the north.

Mutley Plain lies on the route of an ancient road linking Bilburgh, a Bronze Age settlement on the coast at Sutton Pool which later formed the nucleus of the city of Plymouth, to the north.

[1] Before the Norman invasion in 1066, the parish of Higher Mutley was owned by a man named Alwin of Tamerton, and Lower Mutley by another man called Goodwin, but at the time of the Domesday Book (1086) both were owned by Odo, whose feudal overlord was Juhel of Totnes.

[citation needed] A tunnel was driven beneath Mutley Plain by the South Devon Railway Company and was opened to traffic on 2 April 1849.

Owing to its proximity to the expanding Plymouth University and the city centre, large numbers of students now live in the area.