The place-name "Haddenham" is derived from the Old English Hædanham, "Hæda's Homestead" or, perhaps Hædingaham, "the home of the Hadding tribe". It is possible that the first villagers were members of the Hadding tribe from Haddenham in Cambridgeshire. It may be that the first Anglo-Saxons to settle in the Vale of Aylesbury were followers of Cuthwulf, from Cottenham in Cambridgeshire, who, according to the Anglo-Saxon Chronicles, marched southwest to the Thames after routing the British at the Battle of Bedcanford in 571. The Domesday Book of 1086 records the manor as Hedreham. In 1142 it was recorded as Hedenham.

From the Norman conquest of England until the Dissolution of the Monasteries the Convent of St Andrew in Rochester, Kent held the manor. The Crown held the manor for the remainder of the reign of Henry VIII. Thereafter it passed to his daughter Elizabeth I.

The village had a Royal charter as a market town between 1294 and 1301. The market was short-lived because the influential manor of Thame objected to losing trade to Haddenham.

Haddenham is one of only three "wychert (or whitchet) villages" in England. Wychert is a method of building with a white clay mixed with straw to make walls and buildings, which are then thatched or topped with red clay tiles.

Haddenham was long a stronghold of radicalism and in particular of the Buckinghamshire Farm Labourers Union established in 1872 by Edward Richardson of Dinton.

Haddenham used to have several more pubs than today. The Anchor and the Eight Bells at Church End are now private houses. The Waggon and Horses in High Street was converted into the Peking Rendezvous Chinese restaurant, but closed in 2013. The Red Lion in Church End also closed in 2013. A developer applied for planning permission to demolish the Red Lion and replace it with housing, but in 2014 Aylesbury Vale District Council rejected the application.

In 1906 the Great Western Railway opened the railway through the parish, with Haddenham railway station to serve the village. In 1963 British Railways closed the station but kept the line open. In 1987 BR opened Haddenham & Thame Parkway station at a new site, a few hundred yards west of the old one. The railway is part of what is now the Chiltern Main Line.

Haddenham is known for its ponds which were used to breed Aylesbury ducks. Breeding has been revived recently on the pond in front of the parish church.