Efforts that are underway to rehabilitate the Florida Bay ecosystem to a more natural state are best guided by a comprehensive understanding of the natural versus human-induced variability that has existed within the ecosystem. Benthic foraminifera, which are well-known paleoenvironmental indicators, were identified in 203 sediment samples from six sediment cores taken from Florida Bay, and analyzed to understand the environmental variability through anthropogenically unaltered and altered periods. In this research, taxa serving as indicators of (1) seagrass abundance (which is correlated with water quality), (2) salinity, and (3) general habitat change, were studied in detail over the past 120 years, and more generally over the past ~4000 years. Historical seagrass abundance was reconstructed with the proportions of species that prefer living attached to seagrass blades over other substrates. Historical salinity trends were determined by analyzing brackish versus marine faunas, which were defined based on species’ salinity preferences. Statistical methods including cluster analysis, discriminant analysis, analysis of variance and Fisher’s α were used to analyze trends in the data. The changes in seagrass abundance and salinity over the last ~120 years are attributed to anthropogenic activities such as construction of the Flagler Railroad from the mainland to the Florida Keys, the Tamiami Trail that stretches from the east to west coast, and canals and levees in south Florida, as well as natural events such as droughts and increased rainfall from hurricanes. Longer term changes (over ~4000 years) in seagrass abundance and salinity are mostly related to sea level changes. Since seawater entered the Florida Bay area around ~4000 years ago, only one probable sea level drop occurring around ~3000 years was identified.