Alternanthera philoxeroides (AP), a highly invasive plant species, poses a serious threat to agriculture, ecological environment. In this study, the methane production properties of the anaerobic co-digestion (coAD) of AP and corn straw (CS) were studied. The interaction effects of total solids content (TS%), biochar, and Fe3O4 on methane yield were evaluated by regression model and response surface method (RSM). The regression model was extremely significant (p < 0.0001). The results show that the order of the effect of three factors on the methane yield of coAD was: TS% > Fe3O4 > biochar. With the aid of RSM, the optimum values of TS%, Fe3O4 and biochar were: 9.67 %, 8.41 g/kg and 5.51 %, respectively. The effects of three factors on the performance of coAD for methane yield were as follows: the content lower than the predicted optimal value was positively correlated with the methane yield, and the content higher than the predicted optimal value was negatively correlated with the methane yield. To improve the methane quality of AP, coAD could be carried out at a lower TS%, biochar and Fe3O4 were added to enhance the methane yield performance. This paper optimized the operational parameters of the coAD of AP and CS, which also provides new strategies for the treatment and utilization of AP.