Hypoxic conditions in the coastal waters off Texas (USA) were observed since the late 1970s, but little is known about the causes of stratification that contribute to hypoxia formation. Typically, this hypoxia is attributed to downcoast (southwestward) advection of waters from the MississippiAtchafalaya River system. Here, we present evidence for a hypoxic event on the inner shelf of Texas coincident with the presence of freshwater linked to high flow of the Brazos River in Texas. These conclusions are based on hydrographic observations and isotopic measurements of waters on the inner shelf near the Brazos River mouth. These data characterize the development, breakdown, and dispersal of a hypoxic event lasting from June through September 2007 off the Texas coast. Oxygen isotope compositions of shelf water indicate that (1) discharge from the Brazos River was the principal source of freshwater and water column stratification during the 2007 event, and (2) during low Brazos River discharge in 2008, freshwater on the Texas shelf was derived mainly from the MississippiAtchafalaya River System. Based on these findings, we conclude that the MississippiAtchafalaya River System is not the sole cause of hypoxia in the northern Gulf of Mexico; however, more data are needed to determine the relative influence of the Texas versus Mississippi rivers during normal and low flow conditions of Texas rivers.