Rare earth-based materials with a large magneto-caloric (MC) effect have aroused significant research interest due to their potential application for cryogenic magnetic refrigeration (MR) technology. In this study, the Cu site Zn-substituted Dy2BaCu1−xZnxO5 oxides were synthesized and systematically investigated concerning the structural, magnetic phase transition, and MC properties. All the Dy2BaCu1−xZnxO5 oxides were found to be single-phased with an orthorhombic crystal structure (space group Pnma). With the increase of Zn content in the Dy2BaCu1−xZnxO5 oxides, the magnetic phase transition (MPT) temperature decreases gradually from 12.1 K to 2.1 K and the nature of MPT changes from first-order to second-order type. Moreover, Zn substitution leads to enhanced MC performance. The maximum magnetic entropy changes, temperature-averaged entropy changes with 5 K-lift, and relative cooling powers under the magnetic field change of 0–70 kOe were evaluated to be 8.49 J/kgK, 9.67 J/kgK and 13.23 J/kgK, 8.38 J/kgK, 9.29 J/kgK, and 13.03 J/kgK and 227.43 J/kg, and 283.63 J/kg and 343.04 J/kg for Dy2BaCu0.75Zn0.25O5, Dy2BaCu0.5Zn0.5O5 , and Dy2BaCu0.25Zn0.75O5, respectively. The observed tunable MPT and enhanced MC performances indicate that the present Dy2BaCu1−xZnxO5 oxides have potential for practical cryogenic MR applications.