Green microalgae can acclimate over short timescales to changing environmental conditions; however, it is unclear how acclimation, or phenotypic adaptation, alters the organism's metabolism and whether there are conserved responses to different stresses. Following six weeks of exposure, Chlamydomonas reinhardtii could tolerate 100 mM Na+, 100 μM Cu2+, and 35 mM PO43− and partially tolerate 25 mM NH4+, 150 mM Na+ and 150 μM Cu2+. Acclimation was coincident with increased growth rate and reduced cellular accumulation of reactive oxygen species (ROS), which was indicative of enhanced ROS scavenging. Fourier transform infrared (FT-IR) spectroscopy demonstrated distinct metabolic fingerprints of acclimated cells for each stress condition in comparison to non-acclimated cells and to non-stressed cells. Carbon allocation varied in response to stress but also following acclimation. In particular, Na+ stress increased intracellular neutral lipid content but this response was significantly reduced in acclimated cells, while carbohydrate content was enhanced in cells acclimated to excess Cu2+. Acclimation of C. reinhardtii to Na+ allowed enhanced tolerance of multiple stresses simultaneously, while the other acclimated cell lines did not display any advantage. While acclimation of C. reinhardtii to different ionic stresses elicits distinct metabolic signatures within the cells, enhanced ROS detoxification appears to be a conserved acclimation response.