<P><B>Abstract</B></P> <P>Microalgae have been considered as one of the most promising biomass resources for the generation of biodiesel, whereas algal residues (AR) after lipid extraction need to be utilized to enhance its economy and sustainability. This study proposed an integrated biochemical method for microalgae <I>Chlorella</I> sp. processing to achieve a high energy yield (12.33 KJ g<SUP>−1</SUP>VS). The microalgae were first pretreated with mixed enzymes for lipid extraction. After that, the AR obtained from the lipid extraction of microalgae was co-digested with energy grass (GR) <I>Pennisetum</I> hybrid for methane production. Results indicated that the lipid yield from microalgae was enhanced by 54.45% with mixed enzymes pretreatment of cellulase, xynalase and pectinase compared to that without enzymatic pretreatment. The maximal methane yield (207.35 ± 15.66 mLCH<SUB>4</SUB> g<SUP>−1</SUP>VS) of AR and GR co-digestion was obtained with the AR and GR VS ratio at 1:3. Energy yields evaluation based on the biodiesel and methane yields indicated that the energy yield for this two-step combined method was 169% higher than that for biodiesel alone. Thus, the proposed integrated approach was verified to be applicable for microalgae processing for energy production.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Chlorella</I> sp. was a promising feedstock for biodiesel and methane production. </LI> <LI> Enzymatic pretreatment effectively improved the lipid yield of microalgae. </LI> <LI> The highest methane yield was obtained in the co-digestion of AR:GR = 1:3. </LI> <LI> Coupled biodiesel and methane produced 169% more energy than biodiesel alone. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>