With the rapid development of wearable electronics, flexible pressure sensors have attracted wide attention in human–computer interaction and intelligent machines. However, it is a challenge to achieve a sensor with high sensitivity, wide measurement range, and wearing comfortability. Here, we develop an oriented electrospinning thermoplastic polyurethane/polyacrylonitrile (TPU/PAN) nanofibers (OETPN) based piezoresistive pressure sensor (PONPS) in which the active layer and the electrode are assembled perpendicularly. The interdigital electrode is fabricated by spraying silver nanowires (AgNWs) on the OETPN through a mask plate. The active layer is composed of OETPN coated with MXene, encapsulated on the electrode by polyurethane (PU) film. The porous structure of nanofibers membrane broadens the measurement range of the sensor. Employing oriented nanofibers as active layer can improve the sensitivity in low pressure, because oriented nanofibers without interweaving nanofibers are more compressible than disordered nanofibers. Electrode prepared using the spraying method creates nanoscale microstructure and increases sensitivity. The perpendicular assembly has greater response between the active layer and the electrode than the parallel assembly to improve the sensitivity. The sensor exhibits high sensitivity (6.71 kPa⁻¹, 0.02–2 kPa) and wide measurement range (0.02–700 kPa). The sensor can detect weak signals such as radial artery. A pressure array constructed precisely represents the distribution of pressure. An intelligent throat is created by combining machine learning algorithms with the PONPS. It can detect and recognize subtle throat vibrations while speaking, achieving recognition accuracy up to 100% using support vector machine (SVM) for five words with different syllables. The fabricated sensor shows promising prospects in personal healthcare and intelligent robots.