Osmotic stress caused by drought, salt or cold decreases plant fitness. Acquired stress tolerance defines the ability of plants to withstand stress following an initial exposure1. We found previously that acquired osmotolerance after salt stress is widespread among Arabidopsis thaliana accessions2. Here, we identify ACQOS as the locus responsible for ACQUIRED OSMOTOLERANCE. Of its five haplotypes, only plants carrying group 1 ACQOS are impaired in acquired osmotolerance. ACQOS is identical to VICTR, encoding a nucleotide-binding leucine-rich repeat (NLR) protein3. In the absence of osmotic stress, group 1 ACQOS contributes to bacterial resistance. In its presence, ACQOS causes detrimental autoimmunity, thereby reducing osmotolerance. Analysis of natural variation at the ACQOS locus suggests that functional and non-functional ACQOS alleles are being maintained due to a trade-off between biotic and abiotic stress adaptation. Thus, polymorphism in certain plant NLR genes might be influenced by competing environmental stresses.