In estuarine systems, informed water resource management decisions rely, in part, on evaluating how changes in freshwater inflow and salinity affect a selected management target (i.e., habitat or organismal changes). This study examined the distribution of Spartina alterniflora and S. cynosuriodes species along the Altamaha River estuary in Georgia in association with an extensive drought, during which time freshwater inflow decreased considerably and salty water encroached into previously brackish areas. Bankside vegetation was surveyed along the length of the estuary at the beginning and end of the drought (2000, 2002), and again in 2004 after flows had increased. In addition, a removal experiment, in which one or the other plant was removed from naturally mixed communities, was conducted during the drought (2001–2002). In all surveys, S. cynosuroides densities decreased at a location that corresponded to where average high tide salinities were > 14 psu, such that the downstream border shifted from approximately 3 to 6 km from the mouth of the river between 2000 and 2002 and then back to 3 km in 2004. Although the peak density of S. alterniflora also shifted upstream between 2000 and 2002, upstream densities were high in 2004 and plant distribution did not correspond with salinity. In the removal experiment, densities and relative % cover of S. alterniflora increased in all treatments (including controls), whereas densities of S. cynosuroides remained relatively constant except in treatments where it was purposely removed. We interpret these results to suggest that S. alterniflora is a strong invader that can expand into new habitat under stressful (increased salinity, low flow) conditions, and that once it is established it can co-exist with S. cynosuroides. The more rapid response of S. cynosuroides (shifts occurred within 2 years) suggests that its downstream limit is a potential indicator of changes in inflow conditions in this system.