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The multidrug-resistant Staphylococcus aureus (MRSA) is one of the most prevalent human pathogens involved in many minor to major disease burdens throughout the world. Inhibition of biofilm formation is an attractive strategy to treat diseases associated with MRSA infection. In the present investigation, a series of functional group diverse (hetero)aryl fluorosulfonyl analogs were designed, synthesized and tested as antibacterial agents against Staphylococcal spp., and as anti-biofilm candidates. Compounds 8, 15, and 67 were found to possess potent in vitro antibacterial activity among this class of sulfonyl fluorides (MIC = 0.818 ± 0.42, 0.840 ± 0.37 and 0.811 ± 0.37 μg/mL respectively). The analogs 8, 15, 36, and 67 exhibited outstanding anti-biofilm properties compared to other available synthetic antibiotics. The efficacy of synthetic analogs displayed membrane-damaging effect and they are also …