<p>Restriction-modification (R-M) systems protect against phage infection by detecting and degrading invading foreign DNA. However, like many prokaryotic anti-phage defences, R-M systems pose a major risk of autoimmunity, exacerbated by the presence of hundreds to thousands of potential cleavage sites in the bacterial genome. <i>Pseudomonas aeruginosa</i> strains experience the temporary inactivation of restriction endonucleases following growth at high temperatures, but the reason and mechanisms for this phenomenon are unknown. Here we report that <i>P. aeruginosa</i> type I restriction endonuclease is degraded and the methyltransferase is partially degraded, by two Lon-like proteases when replicating at &gt;41 °C. This post-translational regulation prevents self-DNA targeting, which is a risk due to stable genomic hypomethylation, as demonstrated by single-molecule, real-time sequencing and TadA-assisted <i>N</i>⁶-methyladenosine sequencing. When cells grown at &gt;41 °C are returned to 37 °C, full genomic methylation does not fully recover for up to 60 bacterial generations, and thus restriction activity remains off for the duration. Our findings demonstrate that type I R-M is tightly regulated post-translationally with a long memory effect that ensures genomic stability and mitigates autotoxicity.</p>