The sedimentary basins of the British Isles, which are surrounded by plate boundaries that have been variously active from Mesozoic to Cenozoic times, provide a natural laboratory for studying the influence of plate-boundary forces on intraplate vertical motions. A synthesis of apatite fission-track analysis (AFTA) data from the Irish Sea basin system and adjacent regions of the western British Isles reveals a series of cooling episodes from the Cretaceous to the Cenozoic (between 120 and 115 Ma, 65 and 55 Ma, 40 and 25 Ma, and 20 and 15 Ma, respectively). Each episode is of regional extent (~106 km2) and represents a major period of exhumation involving removal of up to 1 km or more of section. These exhumation episodes can be correlated with major tectonic unconformities recognized within the sedimentary succession of the NW European Atlantic margin, but across the western British Isles, the substantially higher exhumation means that little corresponding stratigraphic evidence for these events has been preserved. These exhumation episodes correlate closely with key deformation events at adjacent plate boundaries, suggesting a causative link despite the large distances (up to 1500 km) separating the closest plate boundaries from the zones of exhumation at the time of each episode. Similar kilometer-scale erosional events are revealed by thermochronological studies in other intraplate regions around the world adjacent to passive continental margins, e.g., SE Australia, South Africa, Brazil, stressing the widespread occurrence of such episodes. The low-angle unconformities that result from these regional episodes of kilometer-scale burial and subsequent exhumation are often incorrectly interpreted as representing periods of nondeposition and tectonic stability. Our results indicate that many regions conventionally interpreted as areas of long-term stability have undergone kilometer-scale regional exhumation, and that plate-boundary deformation exerts the primary control on such episodes.