This paper reported a facile strategy for the one-pot synthesis of vinyl sulfone (VS) group terminated hydrogel precursors [poly(ethylene) glycol (PEG)-VS] and PEG hydrogels via catalytic oxa-Michael reaction. Nine potential catalysts were investigated for the reaction between PEG and divinyl sulfone, among which 4-dimethylaminopyridine (DMAP) prevailed for its high catalytic activity. DMAP produced PEG-VS with a conversion of more than 90% in 2 h under a solvent-free condition at room temperature, which significantly simplifies the synthesis of PEG-VS. The preparation of PEG hydrogels was realized by adding glycerol as a crosslinker, and the physical and the mechanical properties were easily controlled by changing the crosslinker concentration as well as the PEG chain length. This strategy can also be applied to other polyhydroxy compounds as crosslinkers, and thus, a library of hydrogels with designed structures and desired properties could be prepared. The PEG hydrogels showed good antifouling properties, low cytotoxicity, and ability to release drugs at a tunable rate, indicating versatile potential bioapplications.