We report the first radiometric dates (thermal-ionization mass spectrometry) from late Pleistocene reef deposits from offshore Belize, the location of the largest modern reef complex in the Atlantic Ocean. The results presented here can be used to explain significant differences in bathymetry, sedimentary facies, and reef development of this major reef area, and the results are significant because they contribute to the knowledge of the regional geology of the eastern Yucatán. The previously held concept of a neotectonically stable eastern Yucatán is challenged. The dates indicate that Pleistocene reefs and shallow-water limestones, which form the basement of modern reefs in the area, accumulated ca. 125–130 ka. Significant differences in elevation of the samples relative to present sea level (>10 m) have several possible causes. Differential subsidence along a series of continental margin fault blocks in combination with variation in karstification are probably the prime causes. Differential subsidence is presumably related to initial extension and later left-lateral movements along the adjacent active boundary between the North American and Caribbean plates. Increasing dissolution toward the south during Pleistocene sea-level lowstands is probably a consequence of higher precipitation rates in mountainous southern Belize.