Since 2019, Santé publique France has been tasked with developing an awareness campaign on antibiotics and antibiotic resistance. It conducted a study based on behavioral science to identify a communication strategy. The study drew on a four-step model of behavior change: knowledge, willingness, ability, and action. A review of the literature and discussions with experts helped identify the enablers and barriers specific to each stage. Based on the identified enablers, four communication approaches were defined: side effects of antibiotics, situations in which antibiotics are unnecessary, consequences and mechanisms of antibiotic resistance, and the unique nature of antibiotics. Each approach was tested in two versions during an 8-arm randomized trial involving 3,987 adults in October 2021. Messages that reinforced the proper use of antibiotics by including concrete situations in which antibiotics are unnecessary performed best for the “know” and “act” stages of the model. However, there is still a need to strengthen the sense of personal involvement and responsibility in the fight against antibiotic resistance. Similarly, misconceptions remain deeply entrenched and must be addressed. The awareness campaign launched in late 2022 adopted the identified communication approach, and the quantitative study conducted following the campaign confirmed the positive perception among respondents.