The reaction of Cu-clusters with a polar and a mixed terminated single crystalline ZnO-substrate upon thermal treatment in UHV is studied in comparison with Au-films. Scanning tunneling microcopy and spectroscopy in combination with photoemission experiments reveal the geometrical and chemical changes in the Cu-cluster system on ZnO(0001)-Zn and ZnO(100) upon annealing up to 770 K. On ZnO() the Cu-clusters show a roof like outline with Cu(111) side facets. The data points to a Cu(110) interface with the ZnO-substrate. The interface of the Cu-clusters and the ZnO-substrate was investigated by the controlled removal of clusters using STM-tip manipulation exposing the “footprints” of the clusters. On both investigated ZnO surfaces an entrenching of the Cu-clusters during annealing was found which partly explains the observed decrease of the amount of Cu visible above the ZnO-substrate level upon annealing. Even at higher annealing temperature the main body of the cluster surface is still pure copper. No large scale oxidation or brass formation was found. Scanning tunneling spectroscopy shows an increased density of occupied states at the cluster perimeter which is possibly relevant as an active site in catalysis.