Harpenden is first recorded in an eleventh century deed in which Edward the Confessor granted an estate to Westminster Abbey, consisting of the area around Hwaethamstede (now Wheathampstead) and Herpedene. This district was first settled by the Belgae who arrived in the first century BC, spreading inland and clearing dense prehistoric forests to make small farm clearings, which became the "Ends" and "Greens" which are so numerous locally.

The Belgae were followed by the Romans, who left traces of their occupation in both the river valleys and at Rothamsted. Then came the Anglo-Saxons; they were threatened by the Danes until an agreement of 886 made the River Lea the agreed boundary between them, Saxons to west, Danes to the east.

The church of St. Nicholas in Harpenden was a Chapel-of-Ease from about 1217 until it was enlarged and the existing tower added in 1470. The old church was demolished in 1861 to make way for a larger building. The tower contains a ring of eight bells, the oldest of which dates from 1612. Harpenden remained part of the ecclesiastical parish of Wheathampstead until 1859, but was from the Middle Ages a separate civil parish with its own officials, who were elected annually at the Abbot's Manorial Court, held at Wheathampstead. In 1862, only three years after the long-sought separation from the parish of Wheathampstead, the church was rebuilt to provide accommodation for the growing congregation. For many years the village saw little change. Agriculture was the main occupation of its inhabitants, the area being especially suited to growing wheat. The resulting abundance of good strong straw encouraged in the eighteenth and nineteenth centuries the growth of the straw plait industry, in which most of the women took part. The straw hat trade was centred around Luton and Dunstable; people from neighbouring villages sold their plait to the hat manufacturers, considerably supplementing small agricultural wages.

Situated as it is between Watling Street to the west and the Great North Road to the east, the road through Harpenden was never one of the country's main highways. Consequently the village grew slowly. When railways were being developed all over the country there was little reason for a route through Harpenden. The people of Luton were campaigning for a railway so a branch line was opened from there in 1860 passing through Harpenden at Batford to join the main Great Northern line at Hatfield. Eight years later the Midland Railway opened its main line extension from Bedford to London. Many of the workers on the railway were billeted in the small village of Harpenden which, with its neighbouring hamlets of Hatching Green and Batford and its cluster of farm-workers cottages in the 'Bowling Alley' to the south, was deemed to justify a station of its own as the line was completed. This direct link with the capital, together with the sale in 1882 of an estate of over a thousand acres of land for building, really started the village's development.

The first estate to be built was centred in Milton Road. Now over a hundred years later most of the houses in Milton Road have been replaced by blocks of flats. Houses were built in a variety of styles as the other estates were developed over the years, eventually linking the hamlets of Batford, Southdown and Kinsbourne Green into the pleasant town we know today.

By 1889 the growth of Harpenden justified its elected representative to claim the status of an Urban District Council. In 1974 Local Government reorganisation saw Harpenden become part of the City and District of St. Albans and the successor parish council eventually took the title of Harpenden Town Council.

Harpenden's most prestigious contribution to history is Rothamsted Manor and its Agricultural Research Centre, founded by Sir John Bennet Lawes (1814 - 1900). Acknowledged as 'the father of agricultural science', Sir John's early field experiments on Hertfordshire farms led to the development of the artificial fertilisers on which most modern farmers now depend.