Dinoflagellates, both armored and unarmored, with distinct cell wall difference, are being affected by elevated CO2-induced ocean acidification (OA). However, their specific responses to OA are not well understood. In this study, we investigated the physiological and molecular response of the armored species Prorocentrum obtusidens and the unarmored species Karenia mikimotoi to OA over a 28-day period. The results show that the two species responded differently to OA. Cell growth rate, particulate organic carbon (POC) content, and the activities of C4 pathway enzymes decreased in P. obtusidens under future acidified ocean condition (pH 7.8, 1000 μatm pCO2), but the activities of carbonic anhydrase (CA), ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO), and superoxide dismutase (SOD) increased. Whereas cell growth rate, contents of Chl a and PON, and SOD activity altered insignificantly in K. mikimotoi, but contents of POC and total carbohydrate, and the activity of RubisCO increased while the activities of CA and C4 pathway enzymes decreased. Transcriptomic analysis indicates that genes associated with antioxidative response, heat shock protein, proteasome, signal transduction, ribosome, and pH regulation were up-regulated in P. obtusidens but down-regulated in K. mikimotoi. Notably, the synthesis of soluble organic matter (i.e., spermidine and trehalose) was enhanced in K. mikimotoi, thereby regulating intracellular pH and improving stress resistance. This study highlights the divergent response of the armored and unarmored dinoflagellates to OA, with the unarmored dinoflagellate exhibiting a higher ability to withstand this stressor. Therefore, caution should be exercised when predicting the behavior and the eventual fate of dinoflagellates in the future acidified ocean.