A surface micromachined piezoresistive pressure sensor with a novel internal substrate vacuum cavity was developed. The proposed internal substrate vacuum cavity is formed by selectively etching the silicon substrate under the sensing diaphragm. For the proposed cavity, a new fabrication process including a cavity side‐wall formation, dry isotropic cavity etching, and cavity vacuum sealing was developed that is fully CMOS‐compatible, low in cost, and reliable. The sensitivity of the fabricated pressure sensors is 2.80 mV/V/bar and 3.46 mV/V/bar for a rectangular and circular diaphragm, respectively, and the linearity is 0.39% and 0.16% for these two diaphragms. The temperature coefficient of the resistances of the polysilicon piezoresistor is 0.003% to 0.005% per degree of Celsius according to the sensor design. The temperature coefficient of the offset voltage at 1 atm is 0.0019 mV and 0.0051 mV per degree of Celsius for a rectangular and circular diaphragm, respectively. The measurement results demonstrate the feasibility of the proposed pressure sensor as a highly sensitive circuit‐integrated pressure sensor.