Abstract Aim In vitro study is to evaluate the effect of chewing simulation in different ph solutions on flexural strength of monolithic zirconia. Patients and methods Forty zirconia bars (N = 40) were cut off zirconia disc using IsoMet. Each bar was 2 mm thickness, 25 mm length and 5 mm width. Specimens were divided into four groups (n = 10). The first group (control) was ready for universal test of flexural strength. Second, third, and fourth group were ready for chewing simulation but in different PH solutions acidic, neutral, and alkaline respectively. These solutions were collected from the lab (acidic-PH = 4, alkaline PH = 10). Twenty extracted human premolars (divided vertically into two halves by IsoMet) were collected for study as antagonist material for chewing simulation. After chewing simulation of these groups, the flexural strength was measured for them and SEM. Results Group 1 (control) showed the highest flexural strength with the mean value (745.21 ± 69.47) followed by group 3 (neutral) (720.40 ± 92.47), then group 2 (acidic) (507.56 ± 111.99), and finally group 4 (alkaline) (497.26 ± 172.90) with the least flexure of strength. There was significance between group 1 (control) and group 2 (acidic) and highly significant with group 4 (alkaline). There was no significance with group 3 (neutral). SEM showed that no cracks in control group. Group (2) surfaces were very smooth with amorphous structure showing disperessed small pores. Group (3) air voids were found entrapped between zirconia grains. Group (4) the surface was rough showing large compact flacks’ fragmentation and branched cracks. Conclusions This study clearly illustrates the significance of flexural strength in different pH of an aqueous solution in terms of the chewing of zirconia ceramics. Cyclic loading decreases flexural strength of 4% yttrium zirconia in neutral but not significantly. In alkaline and in neutral there were significant decrease in flexural strength with chewing due to degradation of stabilizers and transformation tetragonal phase to monoclinic phase. This degradation was in alkaline group more than in acidic group.