ABSTRACT Acclimation enables plants to adapt to immediate environmental fluctuations, supporting biodiversity and ecosystem services. However, global changes are altering conditions for plant disease outbreaks, increasing the risk of infections by pathogenic fungi and oomycetes, and often undermining plant immune responses. Understanding the molecular basis of plant acclimation is crucial for predicting climate change impacts on ecosystems and improving crop resilience. Here, we investigated how Arabidopsis thaliana quantitative immune responses acclimates to daily temperature fluctuations. We analyzed responses to the fungal pathogen Sclerotinia sclerotiorum following three acclimation regimes that reflect the distribution areas of both species. Mediterranean acclimation, characterized by broad diurnal temperature amplitudes, resulted in a loss of disease resistance in three natural A. thaliana accessions. Global gene expression analyses revealed that acclimation altered nearly half of the pathogen-responsive genes, many of which were down-regulated by inoculation and associated with disease susceptibility. Phenotypic analysis of A. thaliana mutants identified novel components of quantitative disease resistance following temperate acclimation. Several of these mutants were however more resistant than wild type following Mediterranean acclimation. Notably, mutant lines in the NAC42-like transcription factor did not show a loss of resistance under Mediterranean acclimation. This resistance was linked to an acclimation-mediated switch in the repertoire of NAC42-like targets differentially regulated by inoculation. These findings reveal the rewiring of immune gene regulatory networks by acclimation and suggest new strategies to maintain plant immune function in a warming climate.