Until medieval times, a branch of the river Rhine flowed close to the centre of the town.

(Bronnen voor de geschiedenis van Zeist, deel 1, ed.

In the last quarter of the 17th century, Count Willem Adriaan van Nassau, an illegitimate descendant of Prince Maurice of Orange, acquired the property and built Slot Zeist in the Dutch Classicist style.

Members of the Evangelische Broedergemeente (Evangelical Brethren's Congregation), the Dutch name for the Moravians, settled in Zeist in 1746, building for their community an impressive array of 18th century Classicist houses planned around two squares.

Camp New Amsterdam, (vliegbasis Soesterberg) a former Royal Netherlands Air Force military airbase near this town, was the venue for the Pan Am Flight 103 bombing trial to take place outside the UK, but under Scots law.

For many years the Dutch National Archaeological Research Service (Rijksdienst voor het Oudheidkundig Bodemonderzoek) was housed at Slot Zeist.