The wetting of Ag-5 wt.% CuO (Ag-5CuO) alloy on initial/CuO-coated zirconia toughened alumina (ZTA) composite ceramic in air was studied in detail. The results showed that the contact angle of the Ag-5CuO/ZTA system rapidly decreased from 81° at 970 °C to 45° at 990 °C during the heating process, however, moderate reductions in contact angle were observed in the subsequent heating and temperature holding stages. In comparison with the contact angle of pure Al2O3, an increment of about 4° of the stable contact angle of Ag-5CuO alloy on the heterogeneous ZTA was observed. The reaction between Al2O3 and CuO can reduce the damage of the CuO-rich liquid to ZrO2 in the ZTA substrate. Both oxygen and CuO were helpful in reducing the contact angle of Ag on ZTA and enhancing the bonding of the Ag/ZTA interface. The continuous CuO coating on ZTA and the monotectic liquid containing more CuO in the region near the triple line induced reductions of more than 40° and about 10° in the contact angle, respectively, between the initial and the CuO coating-improved wetting systems.