Since wearable pressure sensors have promising applications in the fields of human physiological signal detection and bionic robots, there is an urgent need for wearable pressure sensors with comprehensive attributes such as high sensitivity and wide detection range. Here, we introduce a facile electrospinning process to fabricate a film composed of thermoplastic polyurethane/carboxyl multiwalled carbon nanotube/V2CTX-MXene (TPU/c-MWCNTs/V2C). This film has high sensitivity and great linearity, designed for flexible piezoresistive sensors. To further enhance sensor performance, we applied a spin-coating of polydimethylsiloxane (PDMS) on the sandpaper surface to create a top substrate with intermittent spinosum structures. Additionally, a layer of TPU fibers was electrospun between the conductive film and the interdigitated electrodes. The assembled components form a flexible piezoresistive sensor with a wide detection range of 0–200 kPa, a high sensitivity of 545.2 kPa−1, a low detection limit of 5 Pa, a short response time of 48 ms, and excellent long-term durability after 7000 loading/unloading cycles, making the piezoresistive sensor highly discriminating for detecting complex human movements. Thanks to the great sensing performance and stable structure, we conducted various demonstrations to capture human physiological signals, including signals of muscle activity and pulse. These findings indicate the potential of the designed flexible pressure sensor for applications in electronic skin and smart devices.