The name Middleton is of Anglo-Saxon origin and it means middle-farm or middle-settlement. Tyas is a Norman family name but there seems to be no evidence that Middleton Tyas once belonged to a family of that name.
The village lies on a substratum of limestone, which has been extensively quarried. Limestone quarrying still takes place at the nearby Barton roundabout. There was also an 18th-century copper mine and works near the village.
Just outside the village is the Middleton Lodge Estate. Middleton Lodge itself was built in 1760 and is a listed building. It also has a number of Grade II listed buildings and of private parkland.
The Church of St Michael and All Angels lies just outside the village on the road towards Moulton. It is an ancient structure, with Norman arches and pillars on the north side, and Early English on the south. It was restored and renovated between 1867-79 under the direction of Sir George Gilbert Scott.
A Primitive Methodist chapel was erected in the village in 1877; only three years later it was sold to the Wesleyans. It is no longer used as a church.