The river red gum (Eucalyptus camaldulensis Dehnh.) inhabits riparian zones and associated floodplains throughout Australia. Following changes to hydrological regime due to river regulation and prolonged drought in south-eastern Australia, river red gum populations within the Murray–Darling Basin have suffered substantial decline. To better understand the effect of drought on river red gum genetic diversity, we examined single nucleotide polymorphism (SNP) variation in 12 candidate genes among six red gum floodplain forest sites in Yanga National Park, which had experienced contrasting levels of drought and associated decline over an eight-year period. We also examined genetic diversity using these markers in five additional river red gum populations from the Murray–Darling Basin to place genetic diversity results from Yanga in a regional context. Tree condition was significantly lower and mortality higher in the most drought affected sites; however, differences in overall genetic diversity and divergence were not detected among sites. No evidence of genetic adaptation in response to drought in this set of candidate genes was detected when differentiation at individual SNP loci was examined. While the overall condition of E. camaldulensis was strongly influenced by hydrological regime, our results suggest the evolutionary potential of floodplain forests in Yanga were not immediately impacted by population decline linked with drought and changes in hydrological regime. We propose that due to low genetic structure among populations in the region, genetic diversity of river red gums within the Murray–Darling Basin might be effectively conserved during periods of extended drought by protecting representative populations.