In the present work, the mutual effect of Nb and Cu on the microstructure of Zr alloys was investigated. When trace amount of Fe element was presented, the precipitation of Nb and Fe, whose amount was below the equilibrium solid solution limitation in α-Zr, were promoted by the appropriate amount addition of Cu element, leading to the lower content of Nb in α-Zr alloys. However, the precipitation of Nb-enriched phase was inhabited by the further addition of Cu amount since the Fe element was consumed by the enrichment of Zr2Cu phase. Meanwhile, Zr2Cu phase in Zr-1.0Cu alloy was significantly refined and uniformly distributed after the addition of Nb element. In the presence of β-Zr secondary phase stabilized by high amount of Nb element, small amount of Cu element tended to be enriched within the β-Zr phase rather than precipitated as Zr2Cu.