Eastern oysters were ecologically and structurally dominant features of the Chesapeake Bay prior to European colonization. Four centuries of harvest pressure, habitat degradation, and, more recently, disease activity have affected extant oyster population demographics. We compared population demographics and age-at-shell length relationships for modern mesohaline James River oyster populations with James River oysters collected in the years 1611 to 1612 by Jamestown settlers. Historic oyster collections made by hand included a more complete demographic than modern samples collected with patent tongs. Historic oysters had significantly faster growth rates than modern oyster populations. Modern oysters larger than 30–40 mm SL or age 1 grow more slowly than historic oysters of comparable ages. Unlike historic oyster populations, modern James River oyster populations are affected by Dermo and MSX. The downward trend observed in the modern age at length relationship (^{Fig. 4B} see later) between 1 to 1.6 y is probably related to the seasonal onset of disease with increasing temperatures. Observed changes in oyster demographics and growth rates across four centuries reflect changes in the environment as well as changes in oyster biology because of chronic pressure from two oyster diseases.