The BIN1 rs744373 single nucleotide polymorphism (SNP) is a key genetic risk locus for Alzheimer's disease (AD) associated with tau pathology. Because tau typically accumulates in response to amyloid beta (Aβ), we tested whether BIN1 rs744373 accelerates Aβ-related tau accumulation. We included two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI], n=153; Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably [BioFINDER], n=63) with longitudinal 18 F-Flortaucipir positron emission tomography (PET), Aβ biomarkers, and longitudinal cognitive assessments. We assessed whether BIN1 rs744373 was associated with faster tau-PET accumulation at a given level of Aβ and whether faster BIN1 rs744373-associated tau-PET accumulation mediated cognitive decline. BIN1 rs744373 risk-allele carriers showed faster global tau-PET accumulation (ADNI/BioFINDER, P<.001/P<.001). We found significant Aβ by rs744373 interactions on global tau-PET change (ADNI: β/standard error [SE]=0.42/0.14, P=0.002; BioFINDER: β/SE=-0.35/0.15, P=.021), BIN1 risk-allele carriers showed accelerated tau-PET accumulation at higher Aβ levels. In ADNI, rs744373 effects on cognitive decline were mediated by faster global tau-PET accumulation (β/SE=0.20/0.07, P=.005). BIN1-associated AD risk is potentially driven by accelerated tau accumulation in the face of Aβ.