Quorum sensing precursors of bacteria interact with microalgae in cultures and indirectly affect the physiology but their profound effect on the lipid and biomass in relation to improving the biofuel competence is one of the potential unexplored areas. The knowledge on the effect of phycospheric bacterial quorum sensing (QS) precursors on the lipid metabolism of microalgae under axenic and xenic conditions is highly restricted. This study endeavored to investigate an independent effect of QS precursors on the selected potential alga Chlorella sp. and unraveled the hidden prospect of QS for improvement of the lipids and identified the differences between the xenic and axenic conditions in the presence and absence of the QS precursors. Results revealed that N-(3-Oxododecanoyl)-L-homoserine lactone and N-(3-Hydroxyoctanoyl)-DL-homoserine lactone changed lipid composition, increased lipid productivity (2–4.5- folds) and biomass productivity (1.96–4.2 folds) under both xenic and axenic conditions of Chlorella sp. Further, selected QS precursors ameliorated fatty acid composition of the biomass that affected the resultant biodiesel properties at the end. N-(3-Hydroxyoctanoyl)-DL-homoserine promoted synthesis of PUFA and phospholipids with higher C18:2n6 compare to control. In contrast, N-3-Oxo-Dodecanoyl-L-Homoserine lactone promoted SFA and neutral lipids with higher C18:00. Upon investigation of the stress physiology of Chlorella sp., it was revealed that the above QS precursors mediate the antioxidant levels and accumulate lipids, while also encourage biomass amelioration