The preparation of biodegradable active packaging materials is still a major challenge. Here, we report the fabrication and characterization of poly(butylene succinate)-based (PBS) films enriched with a natural polyphenolic antioxidant—quercetin. The PBS-based films with various quercetin content (0.05; 0.10; 0.25 and 0.50 pph on PBS) were prepared via a solvent casting method. Physical (optical, mechanical, thermal, moisture and water sorption, water vapor and UV–vis barrier) and biofunctional (antioxidant and antibacterial against Escherichia coli and Staphylococcus aureus) film properties were tested. The migration of quercetin into model food liquid systems was determined. As a result of quercetin addition, significant changes in color, opacity and UV-blocking effect were observed. The presence of the active substance did not significantly affect the thermal properties of the PBS matrix. However, the mechanical properties of the films were slightly decreased. The films exhibited excellent free radicals (DPPH, ABTS, O2−) scavenging and some bactericidal activities. PBS-quercetin films with superior functional properties have many possibilities for active food packaging applications.