It was established by the inhabitants of Oldorp [nl] as their furthest edge.

Menkemaborg at Uithuizen is a 14th-century, brick-built country house, which was substantially altered around 1700.

The Alberda family, the 18th-century occupants, commissioned artists to decorate the interior with impressive chimney-pieces carved with baroque ornaments, and paintings of mythological scenes.

On 17 May 2008, Cardinal Simonis opened the Trail of St James, connecting Uithuizen to Hasselt, Le Puy en Velay, and Santiago de Compostela, creating a modern, northern branch of the Way of St James.

Uithuizen hosted the finish of stage 4 at the 2013 Energiewacht Tour.