Anastomosing rivers, systems of multiple interconnected channels that enclose floodbasins, constitute a major category of rivers for which various sedimentary facies models have been developed. While the sedimentary products of anastomosing rivers are relatively well-known, their genesis is still debated. A rapidly growing number of ancient alluvial successions being interpreted as of anastomosing river origin, including important hydrocarbon reservoirs, urge the development of robust models for the genesis of anastomosis, to facilitate better interpretation of ancient depositional settings and controls. The upper Columbia River, British Columbia, Canada, is the most-studied anastomosing river and has played a key role in the development of an anastomosing river facies model. Two hypotheses for the origin of upper Columbia River anastomosis include the following: (i) downstream control by aggrading cross-valley alluvial fans; and (ii) upstream control by excessive bedload input from tributaries. Both upstream and downstream control may force aggradation and avulsions in the upper Columbia River. In order to test both hypotheses, long-term (millennia-scale) floodplain sedimentation rates and avulsion frequencies are calculated using 14C-dated deeply buried organic floodplain material from cross-valley borehole transects. The results indicate a downstream decrease in floodplain sedimentation rate and avulsion frequency along the anastomosed reach, which is consistent with dominant upstream control by sediment overloading. The data here link recent avulsion activity to increased sediment supply during the Little Ice Age (ca 1100 to 1950 ad). This link is supported by data showing that sediment supply to the upper Columbia study reach fluctuated in response to Holocene glacial advances and retreats in the hinterland. Upstream control of anastomosis has considerable implications for the reconstruction of the setting of interpreted ancient anastomosing systems. The present research underscores that anastomosing systems typically occur in relatively proximal settings with abundant sediment supplied to low-gradient floodplains, a situation commonly found in intermontane and foreland basins.