Salinity is one of the most important abiotic factors in various natural habitats of microbes. Cyanobacteria are the most widely distributed family of photosynthetic microorganisms in environments with fluctuating salinity. In response to salt stress, many cyanobacteria de novo synthesize compatible solutes to maintain osmotic balance in the cell. However, the regulation of intracellular accumulation of these compounds is still not well understood. The freshwater cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942) exclusively accumulates sucrose as a compatible solute upon salt stress and is thus an ideal model microorganism for studying the metabolism of compatible solute dynamics. Here, we focused on elucidating the regulatory mechanisms involved in salt-induced sucrose accumulation in Syn7942. Using a series of physiological and biochemical experiments, we showed that the ionic effect of salt stress plays an important role in inducing sucrose synthesis, whereby elevated ion concentration directly activates the sucrose-synthesizing enzyme sucrose-phosphate synthase and simultaneously inhibits the sucrose-degrading enzyme invertase, resulting in a rapid sucrose accumulation. Thus, we propose a novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of the enzymes synthesizing and degrading compatible solutes. These findings greatly enhance our current understanding of microbial adaptation to salt.IMPORTANCE Most microbes de novo synthesize compatible solutes for adaptation to salt stress or fluctuating salinity environments. However, to date, one of the core questions involved in these physiological processes, i.e., the regulation of salt-induced compatible solute biosynthesis, is still not well understood. Here, this issue was systematically investigated by employing the model freshwater cyanobacterium Synechococcus elongatus PCC 7942. A novel mechanism for cyanobacterial adaption to salt stress and fluctuating salinity, i.e., the ion-induced synergistic modulation of key synthesizing and degrading enzymes of compatible solutes, is proposed. Because the ion-induced activation/inhibition of enzymes is a fast and efficient process, it may represent a common strategy of microbes for adaptation to environments with fluctuating salinity.