Inundation and salinity directly affect plant productivity and processes that regulate vertical accretion in coastal wetlands, and are expected to increase as sea level continues to rise. In the Mississippi River deltaic plain, river diversions, which are being implemented as ecosystem restoration tools, can also strongly increase inundation in coastal wetlands. We used an in situ mesocosm approach to examine how varying salinity (two levels) and inundation rates (six levels) influenced end-of-season above- and belowground biomass of Spartina patens and Spartina alterniflora during the growing season (March–October) in 2011. Above- and belowground biomass was highest in both species at higher elevations when inundation was minimal, and decreased exponentially with decreased elevation and increased flood duration. This negative biomass response to flooding was more pronounced in S. patens than in S. alterniflora, and S. patens also showed stronger biomass reductions at higher salinities. This salinity effect was absent for belowground biomass in S. alterniflora. These findings suggest that even subtle increases in sea level may lead to substantial reductions in productivity and organic accretion, and also illustrate the importance of considering the inundation tolerance of co-dominant species in receiving areas when utilizing river diversions for delta restoration.