Interproximal contact loss (ICL) between zirconia crown and adjacent natural teeth is a common complication that could lead food impaction and compromise the periodontal/peri-implant tissue health and patient’s satisfaction. Both fretting and sliding wear mode can be found in the frictional pair between zirconia crown and interproximal enamel during mastication. In this study, fretting and sliding wear behavior of interproximal enamel against zirconia in artificial silva was investigated. The wear damage of the interproximal enamel in a sliding movement was higher than in a fretting movement. In fretting mode, the running condition fretting map (RCFM) composed of partial slip regime (PSR), gross slip regime (GSR), and mixed fretting regime (MFR) was constructed depending on different normal loads and displacement amplitudes. Intact surface was observed in the PSR. Plastic deformation at contact center and microcracks at contact margin were detected in the MSR. Severe wear damage occurred in the GSR, predominated by microfracture, brittle deformation. Macroparticles generation, fatigue delamination and abrasive wear prevailed in sliding mode. In contrast, enamel debris could be transferred on zirconia surface while the material loss of the antagonist zirconia was negligible in both fretting and sliding test.