The name "Twyford" means "two fords" (Old English 'twifyrd'), which cross the River Itchen and was noted from as early as 963, being also mentioned in the 1086 Domesday Book as 'Tuiforde', belonging to the Bishop of Winchester and containing a church and six watermills.

In Thomas Moule's English Counties 1837 edition, Twyford is referred to as: "on the river Itchin [sic], 3 miles S. from the City of Winchester, contains 169 houses and 1048 inhabitants."

Twyford includes a village school, St. Mary's Primary School, St Mary's Church, a travel agency, a doctor's surgery and pharmacy, a grocer's shop and Post Office, a traditional clockmaker, two public houses, a social club, and other small businesses.

Former pupils include poet Alexander Pope, who was expelled in the early 18th century for lampooning a master in verse.

This road is called the High Street for the most of its route through the village; before completion of the M3 to the west it was the main A333 from Winchester to Portsmouth.

Twyford lies on the chalk at the northern edge of the Hampshire Basin, dipping south from the southern limb of the Winchester anticline.