Material wear significantly impacts the clinical success and longevity of dental ceramic restorations. This in vivo study aimed to assess the wear behavior of IPS Empress^® glass-ceramic inlays and onlays over 14 years, considering the influence of different antagonist materials. Fifty-four indirect restorations of 21 patients were available for comprehensive wear analysis, with complete follow-up data for up to 14 years. Three-dimensional measurements relied on digitized epoxy resin models produced immediately post-insertion (baseline) and subsequently at 2, 4, and 14 years. The occlusal region on the baseline model was delineated for comparative analysis. Three-dimensional superimpositions with models from subsequent time points were executed to assess wear in terms of average linear wear and volumetric loss. Statistical analyses were conducted in R (version 4.4.1), employing Mann–Whitney U tests (material comparisons) and Wilcoxon signed rank tests (time point comparisons), with a significance threshold of p ≤ 0.05. During the entire study period, an increase in wear was observed at each assessment interval, gradually stabilizing over time. Significant differences in substance loss were found between the follow-up time points, both for mean (−0.536 ± 0.249 mm after 14a) and integrated distance (−18,935 ± 11,711 mm³ after 14a). In addition, significantly higher wear was observed after 14 years with gold as antagonist compared to other materials (p ≤ 0.03). The wear behavior of IPS Empress^® ceramics demonstrates clinically acceptable long-term outcomes, with abrasion characteristics exhibiting stabilization over time.