The extractable lipid compositions in four Florida Bay cores were determined in order to understand environmental changes over the last 160 years. The most significant environmental change was recorded by oscillations in the amplitude and frequency of biomarkers during the 20th century. Two seagrass molecular proxies (Paq and the C₂₅/C₂₇n-alkan-2-one ratio) reached a maximum post 1900, suggesting that abundant seagrass communities existed during the 20th century. A sharp drop in the Paq value from 0.65 to 0.48 in the central Bay at about 1987 seems to reflect seagrass die-off. The concentrations of microbial biomarkers (C₂₀ HBIs, C₂₅ HBIs and dinosterol) substantially increased after 1950 in the TC, BA and NB cores, reflecting an increase in algal (planktonic organism) primary productivity. However, the RB core presented the highest abundance of C₂₅ HBIs and dinosterol during the period of 1880–1940, suggesting historically large inputs from diatoms and dinoflagellates. A substantial rise in abundance of taraxerol (a specific biomarker of mangroves) from 20 μg/g TOC in the 1830s to 279 μg/g TOC in the l980s is likely a result of increased mangrove primary productivity along the shore of the NE Bay. These changes are most likely the result of hydrological alterations in South Florida.