0.5Ba(Zr0.2Ti0.8)O30.5(Ba0.7Ca0.3)TiO3 (BZT-BCT) is a promising lead-free piezoelectric ceramic with excellent piezoelectric properties (e.g., d33 > 600 pC/N). As potential device applications are considered, the electric fatigue resistance of the ceramic must be evaluated. In this Letter, electric-field in situ transmission electron microscopy is employed to study the microstructural evolution in the BZT-BCT polycrystalline ceramic during unipolar cycling. It is shown that the large ferroelectric domains are disrupted and replaced with accumulated defect clusters and fragmented domains after 5 × 104 unipolar cycles. In this fatigued state, the grain becomes nonresponsive to applied voltages.