ABSTRACT Nanowire bioelectronic sensors offer extraordinary sensitivity and real‐time transduction, with silicon being the primary material for device realization. For all nanowire‐based ion‐sensitive field‐effect transistors (ISFETs), direct electrolyte contact or passivation by amorphous dielectrics often introduces interfacial traps leading to instabilities, reduced capacitive control, and poor switching. In this work, we fabricated performance‐enhanced ISFETs from ultrathin, highly crystalline tellurium nanowires (TeNW), which are known for their unique, quasi one‐dimensional (1D) van der Waals structure. The TeNW networks were passivated with ultra‐thin films of insulating graphene oxide (GO). This van der Waals integration enabled high‐performance ISFET arrays, which exhibit strongly enhanced p‐type field‐effect characteristics, clearly outperforming TeNW ISFETs with direct electrolyte contact and those passivated by amorphous silicon dioxide. We account for this performance enhancement by a van der Waals interaction between the 1D TeNW and 2D GO. The resulting TeNW/GO‐ISFETs demonstrate stable operation in phosphate‐buffered saline, while exhibiting apparent pH sensitivities of up to 290 mV/pH, significantly exceeding the Nernstian limit as an effect of the van der Waals interaction. Our findings demonstrate that this van der Waals integration is a viable strategy for performance‐enhanced tellurium ISFETs, paving the way for next‐generation bioelectronics in healthcare diagnostics and environmental monitoring.