The toponym is derived from the Old Englishmixen-burgh, meaning "fortification near dung-heap". "Burgh" refers to Beaumont Castle, which was built about 1100. It no longer stands, but its earthworks remain at the north end of the village. The Domesday Book records that in 1086 Roger d'Ivry held a manor of 17 hides at Missberie. The manor was part of the Honour of St. Valery by 1213, when Robert de St. Valery gave Mixbury's mesne lordship to the AugustinianOsney Abbey. The abbey retained Mixbury until it was suppressed in the Dissolution of the monasteries in 1539.
An open field system of farming prevailed in the parish until 1730. Evidence suggests that it may have begun with two fields, but by the latter part of the 17th century it had been reorganised as a more efficient three-field system. The fields were Middle Field, Sandfield and West Field. Mixbury's inclosure act was passed in 1729 and the inclosure award was made the next year. This is by far the earliest inclosure act for an Oxfordshire parish: the next was not passed until 1758. The area enclosed under the act was about ; land enclosed before 1729 by agreement without the need for an act had been about. The main road between Buckingham and Banbury passes through the parish south of the village. It was made into a turnpike by an Act of Parliament in 1744. The rector had the village school built in 1838. In 1928 it was reorganised as a junior school and older pupils were transferred to the school at Fringford. It was reorganised as an infants' school in 1948 and closed in 1955. The original village consisted of thatch-roofed rubblestone cottages clustered between All Saints and the stream. In 1874 they were demolished under an order of the Court of Chancery and replaced with two rows of brick-faced semi-detached estate cottages laid out as a model villagealong the road leading south from the church.
Railways
In 1847–50 the Buckinghamshire Railway built its branch line to through the northern part of the parish along the Great Ouse Valley. station was built on the line about northeast of the village. The Great Central Main Line from to London Marylebone was built through the eastern part of the parish in the 1890s and opened in 1899. The nearest station was Finmere for Buckingham, about southeast of Mixbury. Buckingham already had a railway station on the Buckinghamshire Railway, and was almost from the Great Central station, so the name was later shortened to the more appropriate "Finmere". In 1961 British Railways closed Fulwell and Westbury station to passenger traffic. In 1963 The Reshaping of British Railways report recommended that BR close both the branch line to Banbury and the Great Central Main Line. It closed Finmere station and the Banbury branch line immediately, and the Great Central Main Line in 1966.