Fisheries encompass complex interplays between social, economic, and environmental factors, but limitations on historical fisheries data can hamper efforts to identify and contextualize the long-term spatiotemporal patterns that shape them. We integrate 2500 years of stable isotope (δ³⁴S, δ¹³C, and δ¹⁵N) and zooarchaeological evidence from Gulf of Mexico fisheries to assess cultural, demographic, and technological changes affecting sheepshead (Archosargus probatocephalus) populations and fishing practices in Louisiana, USA. Concurrent with human population growth, average sizes of sheepshead caught decreased from the 1720s to 1830s. The size of fish caught after the 1830s increased to pre-1720 levels at the same time that isotopic compositions of fish bone collagen show that fish were being caught from a more diverse range of ecosystems, including distant seagrass beds. Our findings provide the first evidence for large-scale depressions of historical sheepshead populations and the processes driving them, including rapid human population growth and sustained harvesting pressure.