This presentation integrates theoretical modeling and experimental investigations to elucidate how surface gel layers formed via oxygen-inhibited free-radical polymerization enhance the lubricity and protective functions of hydrogels in biomedical applications, including in contact lenses. Our theoretical model reveals that speed-invariant shear stress in biological aqueous lubrication arises from localized fluidization due to concentration gradients within the gel network, leading to a monotonic decrease in viscosity toward the high shear-rate plateau (η ∞ ); notably, the shear-thinning exponent is not critical for speed invariance, and the optimal gradient for maintaining lubricity is the weakest possible. Guided by these insights, we experimentally manipulated the surface structure of 17.5 wt. % polyacrylamide hydrogels by varying environmental oxygen concentrations during polymerization, creating preswollen surface gel layers that reduced the friction coefficient tenfold (from μ = 0.021 ± 0.006 to μ = 0.002 ± 0.001) without significantly altering the reduced elastic modulus within the bulk (E* ≈ 200 kPa). A quantitative model based on polymerization kinetics predicted the monomer conversion gradient, aiding the design of hydrogels with tailored surface profiles. Further, by polymerizing hydrogels in molds with varying oxygen permeability—borosilicate glass, polyetheretherketone (PEEK), and polytetrafluoroethylene (PTFE)—we produced hydrogel probes with surface elastic moduli over 100 times lower (E* ≈ 80–106 Pa) than those from glass molds (E* ≈ 31,560 Pa). These hydrogels with surface gel layers significantly reduced frictional shear stresses (τ ≈ 22–35 Pa) and enhanced cellular protection when tested against human telomerase-immortalized corneal epithelial cell monolayers, compared to hydrogels without such layers (τ ≈ 68 Pa). Collectively, our integrated approach underscores the pivotal role of surface gel layers in hydrogel-based lubrication and tissue protection, demonstrating that controlling polymerization conditions—specifically oxygen concentration and mold material—enables the engineering of hydrogels that mimic the protective mucin gel networks of epithelial tissues, with significant implications for designing biomedical devices like contact lenses where reduced friction and enhanced biocompatibility are critical.