Suction caissons are being increasingly considered as an alternative foundation type to monopiles for offshore wind turbines. Single caisson foundations (or monopods) for offshore wind turbines are subjected to lateral cyclic loading from wind and waves acting on the structure. Recent studies have considered the response of suction caissons to such loading in sand, but have generally been limited to a few thousand cycles, whereas offshore wind turbines will generally experience millions of loading cycles over their lifetime. This paper presents the results from a programme of caisson tests in sand, clay and sand over clay seabed profiles, where each test involved about one million cycles of lateral load. The capacity and rotation response is shown to approach that measured in the sand seabed when the sand–clay interface is located at or beneath the caisson skirt tip. In contrast to previously published studies in sand, one-way cyclic loading is the most onerous loading symmetry for a layered seabed with a sand thickness equal to half the skirt length. However, the rotation for this seabed profile is essentially identical if the load is sustained or cyclic, provided that the cyclic loading remains one way. Lateral cyclic loading was seen to increase caisson capacity by up to 30% – with a bias towards clay-dominated seabed profiles – and stiffness by up to 50%. Such stiffness increases need to be considered when assessing the system dynamics for the offshore wind turbine, as demonstrated in the paper.