Atrial fibrillation (AF) is the most prevalent sustained cardiac arrhythmia. Several conditions sensitize to AF, most of which involve inflammation. Here we show sustained, low levels of IL-1β, suffice to sensitize to AF. We found low grade systemic inflammation in mice 15 days after the onset of IL-1b injections, a pattern like that found in AF patients. IL-1β increased caspase-1 maturation in left atria (LA), in a positive feedback loop. Injections of IL-1β in mice shortened action potential (AP), produced a faster restitution of both AP and Ca2+ transient. In addition, an increased fibrosis and enriched β-pleated proteins was found in LA. IL-1β injections sensitized to LA triggered activity (TA) and to AF. Prolongation of AP and the lack of caspase-1 or IL-1R inhibited sensitization to TA. Caspase-1 and IL-1R knockout mice could not be sensitized to AF by IL-1β injections, indicating it depends on IL-1R and caspase-1 expression. We propose a new model of pacing-induced AF, solely elicited by a key immune molecule, IL-1β. Our findings reveal a mechanism of AF induction by IL-1β, offering several new therapeutical targets to be tested, particularly in conditions in which IL-1β and AF are associated, such as gout, diabetes mellitus, obesity, and hypertension.