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Abstract The sulfur fluoride exchange (SuFEx) reaction is significant in drug discovery, materials science, and chemical biology. Conventionally, it involves installation of SO₂F followed by fluoride exchange by a catalyst. We report catalyst‐free Aza‐Michael addition to install SO₂F and then SuFEx reaction with amines, both occurring in concert, in microdroplets under ambient conditions. The microdroplet reaction is accelerated by a factor of ∼10⁴relative to the corresponding bulk reaction. We suggest that the superacidic microdroplet surface assists SuFEx reaction by protonating fluorine to create a good leaving group. The reaction scope was established by performing individual reactions in microdroplets of 18 amines in four solvents and confirmed using high‐throughput desorption electrospray ionization experiments. The study demonstrates the value of microdroplet‐assisted accelerated reactions in combination with high‐throughput experimentation for characterization of reaction scope.