Developing emerging technologies in Internet of Things and artificial intelligence requires high-speed, low-power, high-sensitivity, and switchable-functionality strain sensors capable of sensing subtle mechanical stimuli in complex ambience. Resonant tunneling diodes (RTDs) are the good candidate for such sensing applications due to the ultrafast transport process, lower tunneling current, and negative differential resistance. However, notably enhancing sensing sensitivity remains one of the greatest challenges for RTD-related strain sensors. Here, we use piezotronic effect to improve sensing performance of strain sensors in double-barrier ZnO nanowire RTDs. This strain sensor not only possesses an ultrahigh gauge factor (GF) 390 GPa⁻¹, two orders of magnitude higher than these reported RTD-based strain sensors, but also can switch the sensitivity with a GF ratio of 160 by adjusting bias voltage in a small range of 0.2 V. By employing Landauer–Büttiker quantum transport theory, we uncover two primary factors governing piezotronic modulation of resonant tunneling transport, i.e., the strain-mediated polarization field for manipulation of quantized subband levels, and the interfacial polarization charges for adjustment of space charge region. These two mechanisms enable strain to induce the negative differential resistance, amplify the peak-valley current ratio, and diminish the resonant bias voltage. These performances can be engineered by the regulation of bias voltage, temperature, and device architectures. Moreover, a strain sensor capable of electrically switching sensing performance within sensitive and insensitive regimes is proposed. This study not only offers a deep insight into piezotronic modulation of resonant tunneling physics, but also advances the RTD towards highly sensitive and multifunctional sensor applications.