Wearable pressure sensors have attracted widespread attention in recent years because of their great potential in human healthcare applications such as physiological signals monitoring. A desirable pressure sensor should possess the advantages of high sensitivity, a simple manufacturing process, and good stability. Here, we present a highly sensitive, simply fabricated wearable resistive pressure sensor based on three-dimensional microstructured carbon nanowalls (CNWs) embedded in a polydimethylsiloxane (PDMS) substrate. The method of using unpolished silicon wafers as templates provides an easy approach to fabricate the irregular microstructure of CNWs/PDMS electrodes, which plays a significant role in increasing the sensitivity and stability of resistive pressure sensors. The sensitivity of the CNWs/PDMS pressure sensor with irregular microstructures is as high as 6.64 kPa−1 in the low-pressure regime, and remains fairly high (0.15 kPa−1) in the high-pressure regime (~10 kPa). Both the relatively short response time of ~30 ms and good reproducibility over 1000 cycles of pressure loading and unloading tests illustrate the high performance of the proposed device. Our pressure sensor exhibits a superior minimal limit of detection of 0.6 Pa, which shows promising potential in detecting human physiological signals such as heart rate. Moreover, it can be turned into an 8 × 8 pixels array to map spatial pressure distribution and realize array sensing imaging.