Abstract: Performance degradation shortens the life of solid oxide fuel cells in practical applications. Revealing the degradation mechanism is crucial for the continuous improvement of cell durability. In this work, the effects of cell operating conditions on the terminal voltage and anode microstructure of a Ni–yttria-stabilized zirconia anode-supported single cell were investigated. The microstructure of the anode active area near the electrolyte was characterized by laser optical microscopy and focused ion beam-scanning electron microscopy. Ni depletion at the anode/electrolyte interface region was observed after 100 h discharge tests. In addition, the long-term stability of the single cell was evaluated at 700°C for 3000 h. After an initial decline, the anode-supported single cell exhibits good durability with a voltage decay rate of 0.72%/kh and an electrode polarization resistance decay rate of 0.17%/kh. The main performance loss of the cell originates from the initial degradation.