Iron-containing mesostructured silica (Fe2O3/SBA-15) was prepared and used as heterogeneous catalyst in the integrated sono–photo-Fenton process. The effect of hydrogen peroxide concentration, initial pH, Fe2O3/SBA-15 loading, ultrasonic power, and initial solution concentration on the decolorization of C.I. Acid Orange 7 (AO7) by the integrated heterogeneous sono–photo-Fenton process was investigated in order to optimize process efficiency. The results showed that the decolorization efficiency increased with the increase of hydrogen peroxide concentration, ultrasonic power, Fe2O3/SBA-15 loading, but decreased with the increase of initial pH and initial dye concentration. Catalyst stability was evaluated by measuring iron leaching in solution. The particles size distribution of spent catalyst evidenced a remarkable size reduction during reaction, leading to more reactive surface and higher mass transfer rate. The main reaction intermediates were separated and identified using GC–MS and a possible degradation pathway was proposed.