Fraunhofer EMFT’s research and manufacturing portfolio includes piezoelectrically actuated silicon micro diaphragm pumps with passive flap valves. Research and development in the field of microfluidics have been dedicated for many years to the use of micropumps for generating positive and negative pressures, as well as delivering various media. However, for some applications, only small amounts of fluid need to be pumped, compressed, or evacuated, and until now, only macroscopic pumps with high power consumption have been able to achieve the necessary flow rate and pressure, especially for compressible media such as air. To address these requirements, one potential approach is to use a multistage of high-performing micropumps optimized to negative pressure. In this paper, we present several possible ways to cascade piezoelectric silicon micropumps with passive flap valves to achieve these stringent requirements. Initially, simulations are conducted to generate negative pressures with different cascading methods. The first multistage option assumes pressure equalization over the piezo-actuator by the upstream pump, while for the second case, the actuator diaphragm operates against atmospheric pressure. Subsequently, measurement results for the generation of negative gas pressures down to −82.1 kPa relative to atmospheric pressure (19.2 kPa absolute) with a multistage of three micropumps are presented. This research enables further miniaturization of many applications with high-performance requirements for micropumps, achievable with these multistage systems.