A flexible pH sensor based on using iridium oxide (IrOx) as the sensing film was developed by the roll-to-roll (R2R) process. The inert and biocompatible properties of IrOx make it a desired metal oxide for pH-sensing applications. The flexible substrates being continuously processed by the R2R technique provides the advantages of scalability, reconfigurability, resiliency, on-demand manufacturing, and high throughput, without the need for vacuum systems. Potential sweeps by cyclic voltammetry across the IrOx film against commercial and planar Ag/AgCl electrodes validated the reversible electrochemical mechanisms. Multiple IrOx electrodes showed similar output potentials when continuously tested in the pH range of 2–13, indicating good fabrication uniformity. For practical applications, planar IrOx/Ag-AgCl pairs developed on polyimide substrates were tested, with a good linear fit within pH 2–13, achieving Nernstian responses of around −60.6 mV/pH. The pH sensors showed good repeatability when analyzed with hysteresis, drift, fluctuation, and deviation as the stability factors. The selectivity of the interference ions and the effect of temperature were studied and compared with the reported values. The electrodes were further laminated in a process compatible with the R2R technique for packaging. The flexible sensors were tested under flat and curved surface conditions. Tests in artificial sweat and viscous solutions were analyzed in the Clarke error grid, showing reliable pH-sensing performance. The materials used during the manufacturing processes were sustainable, as the active materials were in small amounts and there was no waste during processing. No toxic chemicals were needed in the fabrication processes. The cost-effective and efficient materials and the fabrication process allow for rapid production that is necessary for disposable and point-of-care devices. Flexible electronics provide a platform for device and sensor integration and packaging, which enables Internet-of-things (IoT) network applications.