We reconstructed middle to late Holocene changes in atmospheric circulation patterns and vegetation in north-west Europe by applying novel geochemical techniques to the sediment record of Lake Uddelermeer (The Netherlands). A comparison of higher plant-derived leaf wax n-alkane distributions archived in the lake sediments with those in living plant material, combined with palynological analysis, indicates that the vegetation immediately surrounding the lake became more open at 3150 cal a BP, while the regional vegetation responded more gradually and ∼650 years later. Our record of the hydrogen isotopic composition of plant leaf waxes (δDwax) shows a deuterium enrichment starting from 3500 cal a BP, which we interpret as a change in atmospheric circulation. A similar δDwax record from nearby Meerfelder Maar (Germany) shows an opposite trend around this time, which could be explained by a change in sea-level pressure resembling a negative North Atlantic Oscillation phase. This could account for depleted δD values of precipitation at Meerfelder Maar, while confounding factors related to the more maritime position of Uddelermeer cause the opposite shift there.