The practical flow protocol presented in this study enables the safe and efficient generation of the coveted gaseous SO2F2 reagent, as well as high reaction rates of the subsequent SuFEx ligation, with wide applicability to various substrates, including therapeutically relevant small molecules, peptides, and proteins. Based on these findings, we believe that this protocol opens up new opportunities in the field of SuFEx click chemistry. In particular, the use of this flow process makes sulfuryl fluoride a viable reagent for installing the -SO2F handle on a variety of phenol and amino functionalities.