Shifts in global seawater 187Os/188Os and 87Sr/86Sr are often utilized as proxies to track global weathering processes responsible for CO2 fluctuations in Earth history, particularly climatic cooling during the Cenozoic. It has been proposed, however, that these isotopic records instead reflect the weathering of chemically distinctive Himalayan lithologies exposed at the surface. We present new zircon (U‐Th)/He thermochronometric and detrital zircon U‐Pb geochronologic evidence from the Himalaya of northwest India to explore these contrasting interpretations concerning the driving mechanisms responsible for these seawater records. Our data demonstrate in‐sequence southward thrust propagation with rapid exhumation of Lesser Himalayan strata enriched in labile 187Os and relatively less in radiogenic 87Sr at ∼16 Ma, which directly corresponds with coeval shifts in seawater 187Os/188Os and 87Sr/86Sr. Results presented here provide substantial evidence that the onset of exhumation of 187Os‐enriched Lesser Himalayan strata could have significantly impacted the marine 187Os/188Os record at 16 Ma. These results support the hypothesis that regional weathering of isotopically unique source rocks can drive seawater records independently from shifts in global‐scale weathering rates, hindering the utility of these records as reliable proxies to track global weathering processes and climate in deep geologic time.