Aim: Newer zirconia materials may have greater strength degradation under cyclic fatigue with increased yttria and cubic content. The purpose of this study was to evaluate the flexural strength (FS) degradation of newer zirconia materials compared to more traditional tetragonal zirconia materials. Materials and methods: The following materials were tested: two 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) materials (Lava Plus, 3M ESPE; Katana ML, Kuraray), one 4 mol% partially stabilized zirconia (4Y-PSZ) material (Katana STML, Kuraray), two 5 mol% partially stabilized zirconia (5Y-PSZ) materials (Katana STML, Kuraray; Lava Esthetic, 3M ESPE), and one lithium disilicate material (IPS e.max CAD LT, Ivoclar Vivadent). Thirty beams were milled for each ceramic material with final dimensions of 4.0 × 1.3 × 18.0 mm after sintering or crystallization. Each specimen was placed on a 3-point bend test device on a universal testing machine (Instron, Norwood, MA). Flexural strength was determined on 10 beam specimens per group with a central load applied until fracture. Flexural fatigue strength was then measured on the remaining 20 beam specimens per group using the staircase method for 6,000 cycles at 2 Hz. Data were analyzed with one-way ANOVAs/Tukey post hoc tests (α = 0.05). Results: A significant difference was found between groups (p < 0.001) per property. The 3Y-TZP zirconia materials had the greatest flexural and flexural fatigue strength. The cubic containing zirconia materials performed more moderately. The lithium disilicate material had the lowest strength values. The percent degradation in flexural fatigue strength of the 3Y-TZP zirconia materials was less than the 5Y-PSZ, Katana UTML, and the 4Y-PSZ, Katana STML, cubic containing materials, but similar to the 5Y-PSZ cubic containing material, Lava Esthetic. Conclusion: The amount of strength degradation was material dependent, with the 4Y-PSZ or 5Y-PSZ cubic containing zirconia materials demonstrating greater or similar strength degradation compared to the primarily tetragonal 3Y-TZP zirconia materials. Clinical significance: The differences in FS degradation between cubic containing materials and traditional zirconia materials could significantly impact the long-term success of these newer materials. Clinicians should be aware that these cubic containing materials may perform differently long-term than the very strong traditional 3Y-TZP materials and to follow manufacturer instructions on required material thickness and indications for use to prevent premature failure of the restoration.