Analysis of detrital zircon U-Pb ages from the Phanerozoic sedimentary record of central Colorado reveals variability in sediment transport pathways across the middle of the North American continent during the last 500 m.y. that reflects the tectonic and paleogeographic evolution of the region. In total, we present 2222 detrital zircon U-Pb ages from 18 samples collected from a vertical transect in the vicinity of Colorado’s southern Front Range. Of these, 1792 analyses from 13 samples are published herein for the first time. Detrital zircon U-Pb age distributions display a considerable degree of variability that we interpret to reflect derivation from (1) local sediment sources along the southern Front Range or other areas within the Yavapai-Mazatzal Provinces, or (2) distant sediment sources (hundreds to thousands of kilometers), including northern, eastern, or southwestern Laurentia. Local sediment sources dominated during the Cambrian marine transgression onto the North American craton and during local mountain building associated with the formation of the Ancestral and modern Rocky Mountains. Distant sediment sources characterize the remaining ~75% of geologic time and reflect transcontinental sediment transport from the Appalachian or western Cordilleran orogenies. Sediment transport mechanisms to central Colorado are variable and include alluvial, fluvial, marine, and eolian processes, the latter including windblown volcanic ash from the distant mid-Cretaceous Cordilleran arc. Our results highlight the importance of active mountain building and developing topography in controlling sediment dispersal patterns. For example, locally derived sediment is predominantly associated with generation of topography during uplift of the Ancestral and modern Rocky Mountains, whereas sediment derived from distant sources reflects the migrating locus of orogenesis from the Appalachian orogen in the east to western Cordilleran orogenic belts in the west. Alternating episodes of local and distant sediment sources are suggestive of local-to-distant provenance cyclicity, with cycle boundaries occurring at fundamental transitions in sediment transport patterns. Thus, identifying provenance cycles in sedimentary successions can provide insight into variability in drainage networks, which in turn reflects tectonic or other exogenic forcing mechanisms in sediment routing systems.