Abstract Algal biofuel has been advocated as a sustainable and environmentally friendly renewable energy source. However, intensive chemical usage, high energy consumption, and high operation and maintenance costs associated with current cell disruption methods have been identified as main challenges to cost-effective production of algal biofuel. Viral infection of algae is a natural process that can lyse algal cells under ambient conditions without using chemicals or energy-intensive equipment. This study, for the first time, provides a comprehensive and in-depth evaluation of the feasibility of using viruses to assist algal lipid extraction. Detailed mechanistic studies were conducted to evaluate the impact on mechanical strength of algal cell walls, lipid yield, and lipid distribution when Chlorella sp. were infected by Paramecium bursaria Chlorella virus 1 (PBCV-1). Viral disruption with multiplicity of infection of 10−8 was able to disrupt concentrated algal biomass completely in six days. Our results indicated that viral disruption significantly reduced the mechanical strength of algal cells. Lipid yield with viral disruption increased more than three times compared to no disruption controls and was similar to that of ultrasonic disruption. Moreover, lipid composition analysis showed that the quality of extracted lipids was not affected by viral infection. The results showed that viral infection is a highly cost-effective technique to promote lipid extraction without extensive energy input and chemicals required by existing disruption methods. The results of this study provided new insights in the development of nature-inspired lipid extraction methods for cost-efficient biofuel production.