An ultra-high resolution acoustic reflection survey within Corpus Christi Bay, Texas, reveals numerous oyster reefs that have died off and been buried by subsequent sedimentation. The die-offs occurred in four temporal clusters, as evidenced by nearly coterminous capping horizons across multiple reef heads. These horizons can be correlated to published, calibrated radiocarbon dates (2-σ uncertainty: ± ~900 years) derived from cored sediments, and placed into the stratigraphic context. The reefs began growing with the initial flooding of the bay at ~9600 ybp. The first die-offs are coincident with the transition from upper bay to open bay environment at ~8140 ybp, with the greatest concentration of die-offs seaward. Subsequent die-offs occurred ~7600, 6870, and 5800 ybp, with a seaward-to-landward progression. These ages appear to either post-date or be concurrent with published periods of accelerated sea level rise of ~1–4 m. However, because bay oysters ( Crassostrea virginica) are robust with respect to salinity and depth changes, we cannot directly link die-offs with punctuated sea level rise. We hypothesize instead that reef die-offs are associated with extreme salinity changes caused by droughts, based on observations during the 1950s Texas drought. During that event, bay reefs were colonized by open-ocean species ( Crassostrea equestris), which gradually replaced bay oysters progressing seaward to landward in concentration. Subsequent flooding and rapid freshening of the bay caused massive mortality of the colonizing species. These floods also brought abundant fine-grained sedimentation that could bury reefs before they could be recolonized. Such a sequence of events could explain widespread early Holocene, seaward-to-landward oyster reef die-offs during times of more frequent and severe drought conditions. A plausible climatological link exists between periods of low rainfall in Texas and periods of accelerated melting of the polar ice cap, which could explain the evident correlation between reef die-off and sea level rise.