In order to improve the output performance of multi-chamber piezoelectric pumps, this paper proposes a novel design for a four-chamber series–parallel piezoelectric pump, based on the characteristics that the parallel chamber structure significantly increases the output flow rate, and the series chamber structure effectively improves the output pressure. The theoretical output flow rate and pressure of the four-chamber series–parallel piezoelectric pump were calculated, and a prototype was fabricated. Tests were conducted to compare the liquid transport performance of piezoelectric pumps with three different structures: series, parallel, and series–parallel. The results show that, when transporting liquid, the output flow rate of the four-chamber series–parallel structure increased by up to 13.3% compared to the four-chamber series structure, reaching a maximum of 767 mL/min. Additionally, the maximum output pressure of the series–parallel structure increased by 43.4% compared to the four-chamber parallel structure, reaching 42.3 kPa. The four-chamber series–parallel design combines the advantages of both series and parallel configurations, improving the output performance of the piezoelectric pump and providing a reference for the structural design of multi-chamber piezoelectric pumps.