Ocean warming and acidification interactively affect the coccolithophore physiology and drives major biogeochemical changes. While numerous studies investigated coccolithophore under short-term conditions, knowledge on how different transitional periods over long-exposure could influence the element, macromolecular and metabolic changes for its acclimation are largely unknown. We cultured the coccolithophore Chrysotila dentata, (culture generations of 1st, 10th, and 20th) under present (lowtemperature low-carbon-dioxide [LTLC]) and projected (high-temperature high-carbon-dioxide [HTHC]) ocean conditions. We examined elemental and macromolecular component changes and sequenced a transcriptome. We found that with long-exposure, most physiological responses in HTHC cells decreased when compared with those in LTLC, however, HTHC cell physiology showed constant elevation between each generation. Specifically, compared to 1st generation, the 20th generation HTHC cells showed increases in quota carbon (Qc:29%), nitrogen (Q N :101%), and subsequent changes in C:N-ratio (68%). We observed higher lipid accumulation than carbohydrates within HTHC cells under long-exposure, suggesting that lipids were used as an alternative energy source for cellular acclimation. Protein biosynthesis pathways increased their efficiency during long-term HTHC condition, indicating that cells produced more proteins than required to initiate acclimation. Our findings suggest that the coccolithophore resilience increased between the 1st-10th generation to initiate the acclimation process under ocean warming and acidifying conditions.