This work presents an acetic acid mediated energy-efficient process that integrates mixotrophic cultivation of extremophilic microalga Chlorella sorokiniana at the photobioreactor (macro) scale, with algal lipid accumulation at the molecular (micro) scale, and rapid biomass harvesting at the algal particle (meso) scale, followed by multiple recycling of nutrient-rich harvested broth. Chlorella sorokiniana is grown mixotrophically in Tris-Acetate-Phosphate medium using Tris buffer as nitrogen source, CO2 and acetic acid as inorganic and organic carbon sources, respectively, at light intensities of 5600–11,000 lx and an optimized photoperiod of 18:6 (Light: Dark) in 25-l bubble-column photobioreactors for 138 h. Acetic acid is used as an organic carbon source to integrate the processes occurring at the three scales; acetic acid ionizes to acetate ions in the culture media, which are enzymatically assimilated inside the alga's cytosol to acetyl-CoA that enhance fatty acid synthesis at the molecular scale and biomass yield at the reactor scale. The excess acetate ions in the culture medium react with the ions formed by the hydrolysis of potash alum to form complexes that react with the ions on algal cell surfaces to facilitate rapid flocculation at the meso (particle) scale. This multiscale integration results in maximum biomass and overall productivity 4.16 g/L and 0.70 g/L/day, respectively, with 25.8% lipid content, obtained at 2% CO2 and 11,000 lx, while reducing the harvesting time to 18–28 min, at a harvesting efficiency and cost of 98%, and 0.064$ per kg of dry biomass, respectively. The first and the second recycles of nutrient-rich broth lower the biomass yield by 9.8% and 14.2%, respectively, while increasing the harvesting time by 8.2% and 15.3%, respectively, as compared to fresh broth. Such multiscale integration of algal growth, macromolecular synthesis and biomass harvesting, followed by broth recycling, offers a novel, cost-effective technology for mixotrophic mass cultivation of extremophilic microalgae.