To further evaluate the compatibility of high-density polyethylene (HDPE) with the biofuels included ethanol–gasoline E30 and biodiesel B30, especially the change of mechanical properties of HDPE over soaking time, soaking tests were performed in E30 and B30 fuels at 45°C for 1608 h. Volume/mass change, yield stress, yield elongation, and impact strength of HDPE were measured at different soaking times. In all fuel soaking tests, more fuel absorption occurred between HDPE and fuels than oxidative damage. Due to higher polarity of bioethanol, E30 is less easily absorbed by HDPE than gasoline and causes less volume and mass change of HDPE. Compared with gasoline and E30, diesel and B30 were less likely to be absorbed by HDPE and there was no significant different of HDPE volume and mass change soaked in them. As fuel could be more easily stored in the amorphous phase of the HDPE than in the crystalline phase, the significant increase of yield elongation and little change of yield stress and the absorbed fuel may act as a plasticizer in HDPE. The increase of impact strength was due to the HDPE became more ductile after fuel soaking rather than strength increase. The compatibility research between HDPE and biofuel can help design engineers to evaluate the performance changes of plastic fuel tank products made of HDPE after long-term fuel soaking.