Lakes and lagoons play an important role worldwide, and salinity fluctuations significantly affect their ecosystems. Bay Sivash, the world’s largest hypersaline water body, underwent a sharp change in salinity, induced by the closing of the North Crimean Canal. To monitor a shift in the ecosystem, a study was carried out from 2014 to 2020 at 15 sites of the lagoon. Since the closure of the canal, the average salinity increased from 22 g L−1 (2013) to 94 g L−1 (2020). Suspended solids and dissolved organic matter also increased. When salinity increased above 50 g L−1, the number of taxa significantly decreased; this was a negative linear relation. The increase in salinity significantly changed the structure of zooplankton and benthos. The most dramatic changes occurred with the salinity increase from 25 to 70 g L−1. Chironomidae larvae numbers began to increase greatly in the ecosystem of the bay, and since 2014, they have rapidly increased their contribution to the abundance of benthos and plankton. The concentration of benthic–planktonic species increased in plankton, in particular, in Harpacticoida and Chironomidae. At salinity above 80–90 g L−1, nauplii and adult brine shrimp appeared to become abundant in plankton and benthos. The transit of the ecosystem to a new alternative state occurred.