The development of appropriate reactors is crucial for the production of biodiesel. In this study, a packed-bed reactor system using lipase–Fe3O4 nanoparticle biocomposite catalyst was successfully developed for biodiesel production based on soybean oil methanolysis. Emulsification before methanolysis improved the reaction rate. The lipase–nanoparticle biocomposite showed high activity and stability in the single-packed-bed reactor at an optimal flow rate (0.25 mL min−1). After 240 h of reaction, the conversion rate was sustained as high as 45%. The conversion rate and stability achieved using the four-packed-bed reactor were much higher than those achieved using the single-packed-bed reactor. The conversion of biodiesel was maintained at a high rate of over 88% for 192 h, and it only slightly declined to approximately 75% after 240 h of reaction. The packed-bed reactor system, therefore, has a great potential for achieving the design and operation of enzymatic biodiesel production on the industrial scale.