The objective of this study is to examine the physiomechanical and surface properties of 3D-printed zirconia in comparison to milled zirconia. A total of 80 disc-shaped (14 × 1.5 ± 0.2 mm) specimens (20 milled and 60 3D-printed (at three different orientations; horizontal, vertical, and tilted)) were manufactured from 3-mol% yttria-stabilized tetragonal zirconia. Five specimens per group were evaluated for crystalline phase, grain size, density, porosity, surface roughness, wettability, microhardness, and SEM analysis of the surface. Biaxial flexural strength (BFS) was measured (n = 15) followed by Weibull analysis and SEM of fractured surfaces. Statistical analysis was performed using one-way ANOVA and Tukey’s post hoc test at α = 0.05. All groups showed a predominant tetragonal phase, with a 450 nm average grain size. There was no significant difference between groups with regards to density, porosity, and microhardness (p > 0.05). The tilted group had the highest surface roughness (0.688 ± 0.080 µm), significantly different from the milled (p = 0.012). The horizontal group presented the highest contact angle (89.11 ± 5.22°), significantly different from the milled and tilted (p > 0.05). The BFS of the milled group (1507.27 ± 340.10 MPa) was significantly higher than all other groups (p < 0.01), while vertical and tilted had a similar BFS that was significantly lower than horizontal (p < 0.005). The highest and lowest Weibull modulus were seen with tilted and milled, respectively. Physical properties of all groups were comparable. The surface roughness of the tilted group was higher than milled. The horizontal group had the highest hydrophobicity. Printing orientations influenced the flexural strength of 3D-printed zirconia. Clinical implications: This study demonstrates how the printing orientation affects the physiomechanical characteristics of printed zirconia.