Pseudomonas aeruginosa (PA) is a predominant hospital-acquired pathogen that poses significant challenges in clinical settings due to its resistance to current antibiotic therapies. Combination therapy is under exploration as a means to enhance the efficacy of current medications due to the challenges in developing new antibiotics. This study evaluated the synergistic efficacy of combining ceftazidime (Cz) and ciprofloxacin (Ci) and its potential to mitigate the development of antibiotic resistance in PA exposed to sub-minimal inhibitory concentrations (sub-MICs) of the antibiotics. The checkerboard assay was used to assess the synergy of Ci and Cz by determining fraction inhibitory concentration (FIC). The impact of Ci on the Cz resistance development was examined by continuously exposing PA to sub-MICs of Cz, both with and without the presence of Ci at a concentration of 0.015625 μg/mL, for 14 days. Vice versa, the effect of Cz on the Ci resistance development was performed under the absence or presence of Cz 0.125 μg/mL. The antibiogram of the strains that were exposed to antibiotics was determined using the disc diffusion method. Findings revealed that Ci and Cz had a synergistic effect in inhibiting PA ATCC 9027 (FIC = 0.5). In the combination of Ci-Cz0.125, an effect was observed, albeit insignificant, in reducing resistant development compared to Ci alone. Exposure to Ci alone promoted resistance to Ci but not to antibiotics from other classes. On the contrary, Cz-Ci0.015625 delayed the antibiotic resistance development of PA compared to Cz alone. However, Cz-exposed strains became resistant to Cz as well as to additional β-lactam antibiotics, such as cefepime and piperacillin/tazobactam. In conclusion, Ci and Cz together demonstrated a synergistic effect and delayed antibiotic resistance development in PA.