Application of electrospun fibers for the purpose of loading and controlled release of water-soluble drugs remains a challenge due to their low carrying effect as well as quick and unstable drug release. In this study, we have developed a novel nanogel-electrospinning technology through which more stable loading and prolonged release of water-soluble drugs was achieved. In brief, nanogel particles synthesized from a chloroquine (CQ)-loaded bovine serum albumin (BSA) solution were prepared and then combined with genipin, a crosslinking agent. The nanogel solution was then crosslinked to prepare an electrospinning solution with an inner mesh structure. Finally, the microfibrous membranes were fabricated by electrospinning the solution. Uniform BSA nanogel particles were wrapped in the fiber membrane and the number of particles increased with the increase of BSA and genipin concentrations. In addition to being loaded within the BSA nanogel particles, CQ was distributed in the fibers as well, which could be clearly identified using ultraviolet-visible spectroscopy (UV-Vis). The physical, chemical, and mechanical properties of nanogel-electrospun microfibers were similar to those of microfibers formed through a conventional electrospinning approach. The drug release tests indicated that with the same number of BSA nanogel particles, increased CQ loading resulted in increased initial release of the same. The duration of a single drug release cycle lasted up to 40 days. In conclusion, findings from this study have indicated that nanogel-electrospinning is a convenient and effective technology to achieve controlled long-term release of water-soluble drugs.