AbstractThe practical implementation of memristors in neuromorphic computing and biomimetic sensing suffers from unexpected temporal and spatial variations due to the stochastic formation and rupture of conductive filaments (CFs). Here, the biocompatible silk fibroin (SF) is patterned with an on‐demand nanocone array by using thermal scanning probe lithography (t‐SPL) to guide and confine the growth of CFs in the silver/SF/gold (Ag/SF/Au) memristor. Benefiting from the high fabrication controllability, cycle‐to‐cycle (temporal) standard deviation of the set voltage for the structured memristor is significantly reduced by ≈95.5% (from 1.535 to 0.0686 V) and the device‐to‐device (spatial) standard deviation is also reduced to 0.0648 V. Besides, the statistical relationship between the structural nanocone design and the resultant performance is confirmed, optimizing at the small operation voltage (≈0.5 V) and current (100 nA), ultrafast switching speed (sub‐100 ns), large on/off ratio (10⁴), and the smallest switching slope (SS < 0.01 mV dec⁻¹). Finally, the short‐term plasticity and leaky integrated‐and‐fire behavior are emulated, and a reliable thermal nociceptor system is demonstrated for practical neuromorphic applications.