The Tonto Group of the Grand Canyon is an archetypal record of prolonged sea-level rise and Cambrian biotic evolution. We use a Bayesian age modelling approach to quantify this unique chronostratigraphic record by combining high-precision detrital zircon maximum depositional ages with trilobite biostratigraphy and dynamic time-warped carbon isotope chemostratigraphy to create a vertical and lateral age model through the full stratigraphic sequence across the entire Grand Canyon transect. The results of this modelling test hypotheses related to epeirogenic versus eustatic mechanisms of transgression as well as the accuracy of the current global Cambrian geologic timescale. The Tapeats Sandstone of the Tonto Group is an iconic basal marker of the Sauk II transgression across the Great Unconformity; our age model reveals that its accumulation and distribution along the western Laurentian craton margin were influenced by local tectonics and base-level changes, in addition to global eustatic influences. Early Paleozoic tectonic subsidence of the western Laurentian cratonic margin in the Grand Canyon region did not occur until c. 504 Ma, later than previously thought. Our age model also facilitates numerical calibration of intercorrelated North American and global Cambrian stages and reallocation of time within the Cambrian that has implications for a faster tempo of early animal evolution and associated global carbon cycle perturbations. In addition to refining the depositional history of western Laurentia and the middle Cambrian (Miaolingian) timescale, our approach highlights the utility of data-integrative Bayesian age models for creating radioisotopically calibrated chronostratigraphies.