This paper focuses on the design and fabrication of a high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit, which consists of an encapsulated pressure-sensitive chip, a temperature compensation circuit and a signal-conditioning circuit. A silicon on insulation (SOI) material and a standard MEMS process are used in the pressure-sensitive chip fabrication, and high-temperature electronic components are adopted in the temperature-compensation and signal-conditioning circuits. The entire pressure sensor achieves a hermetic seal and can be operated long-term in the range of −50 °C to 220 °C. Unlike traditional pressure sensor output voltage ranges (in the dozens to hundreds of millivolts), the output voltage of this sensor is from 0 V to 5 V, which can significantly improve the signal-to-noise ratio and measurement accuracy in practical applications of long-term transmission based on experimental verification. Furthermore, because this flexible sensor’s output voltage is adjustable, general follow-up pressure transmitter devices for voltage converters need not be used, which greatly reduces the cost of the test system. Thus, the proposed high-temperature piezoresistive pressure sensor with an integrated signal-conditioning circuit is expected to be highly applicable to pressure measurements in harsh environments.