Heterogeneous KF/CaO catalyst, prepared by the wet impregnation method with different KF loadings (15–35wt.%) and calcination temperatures (600–1000°C), was used to assist biodiesel production from microalgae Chlorella vulgaris under the combination of ultrasound and microwave (US–MW) irradiation. It was found that the catalyst calcinated at 900°C with 25wt.% KF loading presented the optimum performance, when the test was conducted with 12wt.% of catalyst and a methanol to biomass ratio of 8:1 at 60°C for 45min. The highest fatty acid methyl esters (FAME) yield was 93.07±2.39%, which was significantly higher than that achieved by using US or MW irradiation individually. The catalysts were characterized by X-ray diffraction, scanning electron microscopy and Brunauer–Emmett–Teller.