The response of coastal wetlands to sea-level rise (SLR) largely depends on the tolerance of individual plant species to inundation stress and, in brackish and freshwater wetlands, exposure to higher salinities. Phragmites australis is a cosmopolitan wetland reed that grows in saline to freshwater marshes. P. australis has many genetically distinct haplotypes, some of which are invasive and the focus of considerable research and management. However, the relative response of P. australis haplotypes to SLR is not well known, despite the importance of predicting future distribution changes and understanding its role in marsh response and resilience to SLR. Here, we use a marsh organ experiment to test how factors associated with sea level rise—inundation and seawater exposure—affect the porewater chemistry and growth response of three P. australis haplotypes along the northern Gulf of Mexico coast. We planted three P. australis lineages (Delta, European, and Gulf) into marsh organs at five different elevations in channels at two locations, representing a low (Mississippi River Birdsfoot delta; 0–13 ppt) and high exposure to salinity (Mermentau basin; 6–18 ppt) for two growing seasons. Haplotypes responded differently to flooding and site conditions; the Delta haplotype was more resilient to high salinity, while the Gulf type was less susceptible to flood stress in the freshwater site. Survivorship across haplotypes after two growing seasons was 42% lower at the brackish site than at the freshwater site, associated with high salinity and sulfide concentrations. Flooding greater than 19% of the time led to lower survival across both sites linked to high concentrations of acetic acid in the porewater. Increased flood duration was negatively correlated with live aboveground biomass in the high-salinity site (χ2 = 10.37, p = 0.001), while no such relationship was detected in the low-salinity site, indicating that flood tolerance is greater under freshwater conditions. These results show that the vulnerability of all haplotypes of P. australis to rising sea levels depends on exposure to saline water and that a combination of flooding and salinity may help control invasive haplotypes.