This paper presents the first combined Cu and Zn isotopic study of altered oceanic crust at Integrated Ocean Drilling Program (IODP) Hole 1256D that penetrates a volcanic section, a lava‐dyke transition zone, a sheeted dyke complex, and a plutonic complex. In the volcanic section, all but one rocks have Cu and Zn isotopic compositions similar to fresh mid‐ocean ridge basalt (MORB), reflecting restricted seawater circulation and low oxygen fugacity. Rocks in the transition zone have MORB‐like δ65Cu and δ66Zn, indicating the dominant influence of basalt‐derived Cu and Zn during alteration. Rocks in the dyke complex have more variable δ65Cu (−0.50–0.90‰) and δ66Zn (0.19–0.55‰) and those in the plutonic complex have δ65Cu of −0.43 to 0.20‰ and δ66Zn of 0.21 to 0.41‰. The rocks with heavier δ66Zn and heavier or lighter δ65Cu relative to MORB are characterized by Cu‐Zn depletions, low Li/Yb (<1.0) and low δ18O (<5‰), suggesting that hydrothermal extraction during high temperature alteration of oceanic crust can result in significant Cu and Zn isotope fractionation. Such large Cu and Zn isotopic variations are the results of redox transformation of Cu as well as Cu and Zn isotope fractionation between altered basaltic rocks and dissolved Cu and Zn species in hydrothermal fluids (e.g., [CuCl3]1−, Zn(HS)42−). This work is the first to define the distribution of Cu and Zn isotopes in an intact oceanic crust with concentration‐weighted averages of δ65Cu (0.05 ± 0.03‰) and δ66Zn (0.27 ± 0.01‰). The potential implications of these new observations are discussed.