A bstract The purpose of this study was to fully realize the clinical plausibility of a newly introduced yttria gradient monolithic multilayer dental zirconia and the current indication range for dental zirconia; hence, an investigation leading to a comprehensive understanding of the effect of yttria content on the properties of zirconia was undertaken. Each layer from a yttria gradient monolithic multilayer zirconia system with two types (esthetic and functional types, Meiying Zirconia, UPCERA, China) was selected for investigation of its chemical composition by X-ray fluorescence. Layers with yttria content interval of about 0.4 mol%-0.5 mol% were chosen for subsequent testing. Their phase fractions, grain sizes, low-temperature degradation (LTD) resistance, coefficient of thermal expansion (CTE), and mechanical properties were characterized. The yttria content from the occlusal to the gingival region was from 5 mol% to 4.1 mol% and 4.7 mol% to 3.2 mol% for esthetic type and functional type, respectively. Ultimately, we investigated the selected five yttria content layers, 5Y, 4.5Y, 4Y, 3.6Y, and 3.2Y. With increased yttria content, increasing cubic phase fractions (from 25.86 wt% to 58.53 wt%) and mean grain sizes (from 0.31 μm to 0.72 μm) were detected; monoclinic content after LTD decreased; and there was a decreasing tendency for CTE, although no statistically significant difference was found ( F = 2.43, p = 0.117). In addition, yttria dopant showed no effect on elastic modulus ( F = 2.43, p = 0.464) but slightly increased hardness ( F = 4.10, p = 0.014). However, there were notable decreases in fracture toughness ( F = 227.58, p < 0.001), biaxial flexural ( F = 52.31, p < 0.001), and fatigue strength ( F = 56.52, p < 0.001). The percentages of strength degradation from monotonic to fatigue tests were about 33%–40%, independent of yttria doping ( F = 1.82, p = 0.136).