The third-generation semiconductor silicon carbide (SiC) is identified as one of the vitally important candidate materials to serve as a functional unit that performs stably and reliably under harsh working conditions, with respect to its excellent piezoresistive effects and robust physical/chemical characteristics. In the current work, we put forward the fabrication of SiC nanowires with co-doped N and P elements, which were fabricated via the pyrolysis of a polymeric material. The as-grown nanowires have a typical diameter of ∼260 nm with a 10 surface. The measured transverse piezoresistance coefficient π_[10] of the established SiC nanowires increased from 5.07 to −146.30 × 10⁻¹¹ Pa⁻¹ as the loading forces varied from 24.95 to 130.51 nN. Meanwhile, the corresponding gauge factor (GF) was calculated up to ca. −877.79, which is higher than the values for all SiC nanostructures ever reported. The mechanism concerning the giant negative piezoresistance behavior of SiC nanowire is proposed. The current exploration may pave a new avenue for the development of highly sensitive and robust pressure sensors that could survive under harsh working conditions.