The present work aimed to investigate the feasibility of fly ash, a by-product of coal combustion, for enhanced degradation of an azo dye Acid Orange 7 (AO7) under ultrasonic irradiation. X-ray diffraction and energy dispersive X-ray analysis indicated that ultrasonic irradiation did not change the crystal structure of fly ash. The decolorization efficiency of AO7 by the combined process could reach 76.7%, while ultrasonic process alone only removed 3.8% of AO7 within 60 min. A synergetic effect between fly ash and ultrasonic irradiation was firstly observed. The decolorization of AO7 fitted the first-order rate kinetics, and the K1 was 0.0246 min−1 for the combined process. Radical quenching experiment by iso-propanol (ISP) indicated that 24.8% of AO7 decolorization was contributed to hydroxyl radicals, indicating that the contribution of hydroxyl radicals was not as significant as expected. Theoretic analysis revealed that the sizes of fly ash cover the estimated resonance size of cavitation bubbles generated in this experiment. As such, fly ash particles could act as nucleus to generate more cavitation bubbles and enhance the ultrasonic degradation efficiency. Fly ash combined with ultrasonic irradiation has the great potential for practical treatment of wastewater containing organic pollutants.