Flavonoids, a class of natural products with a variety of applications in nutrition, pharmacy and as biopesticides, could substitute more harmful synthetic chemicals that persist in the environment. To gain a better understanding of the biodegradability of flavonoids and the influence of structural features, firstly, the ultimate biodegradation of 19 flavonoids was investigated with the Closed Bottle Test according to the OECD guideline 301 D. Secondly, regarding the fast abiotic degradation reported for several flavonoids with severe concentration decrease within hours and its possible impacts on the processes behind the ultimate biodegradation, primary degradation of 4 selected flavonoids was compared at conditions representing biodegradation, abiotic degradation, and mixed substrates by monitoring the flavonoids' concentrations with HPLC-UV/vis. Our results showed that 17 out of the 19 tested flavonoids were readily biodegradable. Structural features like a hydroxy group at C3, the C2–C3 bond order, a methoxy group in the B ring, and the position of the B ring in regard to the chromene core did not affect biodegradation of the tested flavonoids. Only flavone without any hydroxy groups and morin with an uncommon 2′,4′ pattern of hydroxy groups were non-readily biodegradable. Monitoring the concentration of 4 selected flavonoids by HPLC-UV/vis revealed that biodegradation occurred faster than abiotic degradation at CBT conditions with no other carbon sources present. The presence of an alternative carbon source tends to increase lag phases and decrease biodegradation rates. At this condition, abiotic degradation contributed to the degradation of unstable flavonoids. Overall, as a first tier to assess the environmental fate, our results indicate low risks for persistence of most flavonoids. Thus, flavonoids could represent benign substitutes for persistent synthetic chemicals.