Seismic data and sediment cores from the Galveston estuary complex were used to reconstruct the evolution of the estuary during the Holocene. These data show that the estuary complex has had a history of rapid and dramatic change in response to (1) sea-level rise across the irregular topography of the ancestral Trinity River valley and (2) changes in climate, which regulated sediment supply to the estuary. In general, the valley morphology consists of a deep incision near the center and broad, terraced flanks. As sea level rose during the Holocene and flooded the valley, the shape of the estuary changed from narrow and deep to wide and rounded. As sea level rose to the elevation of the relatively flat fluvial terraces, these areas were flooded rapidly, resulting in expansions in bay area and dramatic reorganization of bay environments. The most notable changes were up-valley shifts in the bayhead delta of tens of kilometers in a few centuries. Radiocarbon ages indicate that these events took place ca. 9600, ca. 8500, and between ca. 7700 and 7400 yr B.P. The early flooding events occurred when sea level was rising rapidly (average 4.2 mm/yr; Milliken et al., this volume, Chapter 1), perhaps episodically. The ca. 8200 yr B.P. flooding surface corresponds to a prominent terrace at −14 m. The ca. 7700–7400 yr B.P. flooding episode was the most dramatic in terms of its impact on the estuary setting. Following this event, the area of the estuary increased by ~30%. This flooding event occurred as the rate of sea-level rise was starting to decrease. The level of this flooding surface also corresponds to a terrace at ~–10 m, but the magnitude of flooding is too large to be explained entirely by flooding of this terrace. At the same time, Matagorda Bay to the west and Sabine Lake to the east experienced similar dramatic flooding events. This event occurred when the climate of east-central Texas was in transition from cool and moist to warm and dry, and the vegetation cover of the region was undergoing a reduction in forest and an increase in grasslands. Hence, the ca. 7700–7400 event was likely amplified by a reduction in sediment supply to the estuary triggered by this regional climatic change coupled with an increase in sediment accommodation space caused by flooding of a terrace. Following the ca. 7700–7400 yr B.P. flooding event, the estuary setting changed relatively little as the rate of sea-level rise decreased to less than 2.0 mm/yr. By ca. 2600 cal yr B.P., the modern Trinity bayhead delta had begun to form. Circa 1600 cal yr B.P., the delta experienced a phase of rapid growth. This more recent episode of delta growth may have resulted from an increase in the rate of sediment supply, perhaps associated with human occupation and agriculture in the drainage basin. More recent anthropogenic changes include accelerated subsidence due to groundwater and hydrocarbon extraction. These changes are occurring at rates that approach those that occurred during prior flooding events of the Holocene. Thus, the Galveston estuary complex could be on the verge of another flooding event that would mainly impact the Trinity bayhead delta and low-lying areas around the delta.