In recent years, early oyster recruitment in Mississippi has been driven by climate-related variability in precipitation, as expressed by alternating periods of extreme wet and dry conditions. Since 2018, commercial oyster landings from western Mississippi Sound have ceased. The primary deterrent to early oyster recruitment shifted from substrate limitation to recruitment limitation in 2019, when oyster spawning stocks were completely decimated by unprecedented freshwater discharge from the Bonnet Carré spillway. This catastrophic event apparently hampered both the supply and survival of oyster larvae. Consequently, early oyster recruitment was effectively eliminated in 2019. Following low and regionally variable levels of early oyster recruitment in 2020, extreme low salinity conditions prevailed again in 2021 due to elevated regional rainfall throughout the oyster recruitment period. In 2023, early oyster recruitment returned to high levels in conjunction with a historic drought. The 2024 discharge regime is expected to be influenced by a La Niña pattern, characterized by dry and warm conditions in the southern US. Thus, for the past six years, early recruitment of oysters has been primarily regulated by climatic extremes. Spat settlement as well as growth and mortality of transplanted hatchery-reared juvenile oysters varied spatially and between years in conjunction with salinity. In addition to direct effects of salinity, covariation in associated biotic factors such as predation intensity, food quality, and disease also contribute to recruitment success. Extreme climatic events in conjunction with multiple stressors continue to limit the recovery of oyster resources in the Mississippi Sound estuary. The development of an adaptive oyster management strategy is essential in the face of current environmental challenges.