Microparticles with multiple internal chambers hold great promise as drug delivery systems due to their ability to sustain the release of drugs with short half-lives. However, conventional batch methods used for their fabrication have limitations in terms of encapsulation efficiency and particle size distributions, while microfluidic methods suffer from low production efficiency. Herein, a batch-microfluidic hybrid method is presented for fabricating poly(DL-lactic-co-glycolic acid) (PLGA) polymeric microparticles with uniformly distributed, multiple inner microchambers. A scalable batch method is utilized for primary water-in-oil (W/O) emulsions, combined with a precise microfluidic approach for generating controlled secondary emulsions. This approach results in highly uniform PLGA microparticles with tunable size and improved encapsulation efficiency. Additionally, the effect of polydopamine-based surface hydrophilic modification of microfluidic channels on drug encapsulation efficiency is investigated, achieving an efficiency of approximately 85%. The prepared multichamber PLGA microparticles exhibit an extended-release profile without initial burst release, demonstrating their potential for sustained drug delivery in various biomedical applications.