A porous and microstructure piezoresistive material composed of polydimethylsiloxane (PDMS) and multiwalled carbon nanotubes (MWCNTs) was designed and prepared for a flexible and highly sensitive pressure sensor over a wide detection range. The microstructure was patterned on the surface of the partially cured PDMS/MWCNTs/NaCl mixture by imprinting a nonwoven fabric. After curing and dissolving the NaCl powders, the porous and surface microstructure PDMS/MWCNT film was obtained. Two PDMS/MWCNT films were stacked together and sandwiched between two copper foil electrodes, in which the two microstructure surfaces were in contact with the electrodes. Due to the synergistic effects of the combination of the porous structure and surface microstructure, the flexible sensor had highly sensitive response over a wide pressure range from 1 Pa to 100 kPa. Under the small pressure, the high sensitivity was achieved by the change in contact areas between the electrodes and the surface microstructures; at high pressure up to 100 kPa, the sensor retained its high sensitivity because of the porous structure of the piezoresistive PDMS/MWCNT material. Additionally, the sensor had fast response speed and good durability. The piezoresistive pressure sensors based on the porous and microstructure PDMS/MWCNTs were demonstrated in detection of sound, monitoring of human activities, and array mapping of the spatial pressure distribution.