It is often said that pnictogen‐bonding catalysis, and σ ‐hole catalysis in general, would not work in aqueous systems because the solvent would interfere as an overcompetitive pnictogen‐bond acceptor. In this study, we show that the transfer of pnictogen‐bonding catalysis from hydrophobic solvents to aqueous systems is possible by replacing only hydrophobic with hydrophilic substrates, without changing catalyst or reaction. This differs from conventional covalent Lewis acid catalysts, which are instantaneously destroyed by ligand exchange. With their water‐proof substituents in place of exchangeable ligands, pnictogen‐bonding catalysts, the supramolecular counterpart of Lewis acid catalysts, are evinced to catalyze transfer hydrogenation of quinolines in neutral aqueous systems. To secure these results, we introduce a water‐soluble fluorogenic substrate that releases a coumarin upon the reduction of quinolines instead of activated quinolidiniums, and stiborane catalysts with deepened σ holes. They demonstrate that pnictogen‐bonding catalysts can operate in higher‐order architectures for supramolecular systems catalysis under biologically relevant conditions, and provide an operational assay for high‐throughput catalyst screening by fluorescence imaging, in situ under relevant aqueous conditions.