Selective aerobic epoxidation of alkenes without any additives is of great industrial importance but still challenging because the competitive side reactions including C═C bond cleavage and isomerization are difficult to avoid. Here, we show fabricating Cu(I) single sites in pristine multivariate metal-organic frameworks (known as CuCo-MOF-74) via partial reduction of Cu(II) to Cu(I) ions during solvothermal reaction. Impressively, CuCo-MOF-74 is characteristic with single Cu(I), Cu(II), and Co(II) sites, and they exhibit the substantially enhanced selectivity of styrene oxide up to 87.6% using air as an oxidant at almost complete conversion of styrene, ∼25.8% selectivity increased over Co-MOF-74, as well as good catalytic stability. Contrast experiments and theoretical calculation indicate that Cu(I) sites contribute to the substantially enhanced selectivity of epoxides catalyzed by Co(II) sites. The adsorption of two O2 molecules on dual Co(II) and Cu(I) sites is favorable, and the projected density of state of the Co-3d orbital is closer to the Fermi level by modulating with Cu(I) sites for promoting the activation of O2 compared with dual-site Cu(II) and Co(II) and Co(II) and Co(II), thus contributing to the epoxidation of the C═C bond. When other kinds of alkenes are used as substrates, the excellent selectivity of various epoxides is also achieved over CuCo-MOF-74. We also prove the universality of fabricating Cu(I) sites in other MOF-74 with various divalent metal nodes.