Metabolic mechanisms driving rapid lipid production in atmospheric and room temperature plasma-mutagenized Chlorella sorokiniana remain unclear, hindering improvement in lipid productivity through genetic modification. This study investigated two dominant strains, ArX13 and AirX12, mutated by argon and air ARTP, for growth, lipid production, and transcriptomic changes across various culture stages. Results showed that biomass and lipid contents peaked in the late stage, with ArX13 and AirX12 achieving final biomass of 0.71 g/L and 0.70 g/L, and lipid content of 58.57 % glipid gbiomass−1 and 46.90 % glipid gbiomass−1, 2.20 and 1.77 times higher than the control, respectively. The maximum biomass and lipid productivity occurred at the mid-stage, with ArX13 and AirX12 showing biomass productivity of 0.025 gbiomass L−1 day−1 and 0.024 gbiomass L−1 day−1, and lipid productivity of 17.79 mglipid L−1 day−1 and 11.40 mglipid L−1 day−1, respectively. Transcriptomic analysis revealed minimal changes of gene expression during early and late stages, but significant biomass and lipid synthesis during the middle stage. Key genes like PDHB, ATP6A, LSC1 and OGDH were identified in the PPI network throughout the culture cycle, with PDHB remarkably promoting lipid precursor production, up-regulated 8.37 and 4.99-fold in M_ArX13-M_X0 and M_AirX12-M_X0, respectively. In addition, high expression of photosynthesis-related genes (psaL, psaO, psaD, psaK, psbP) contributed the superior lipid production for the argon-based ARTP case, highlighting common and intrinsic mechanisms regulating microalgal lipid accumulation under different ARTP mutations. This study shows that the selection of appropriate ARTP gases can maximize the lipid production of microalgal, and the discovery of some key genes can provide a theoretical basis for the selection of target genes for microalgal research, which is of great significance for promoting the research and development of microalgal lipid engineering.