pH monitoring in clinical assessment is pivotal as pH imbalance significantly influences the physiological and extracellular functions of the human body. Metal oxide based pH sensors, a promising alternative to bulky pH electrodes, mostly require complex fabrication, high-temperature post-deposition treatment, and high expenses that inhibit their practical applicability. So, there is still room to develop a straightforward and cost-effective metal oxide based pH sensor comprising high sensitivity and reliability. In this report, a novel solution-processed and low-temperature annealed (220 °C) mixed-valence (vii/vi) oxide of rhenium (RexOy) was applied in an electrolyte–insulator–semiconductor (EIS) structure. The annealing effect on morphological, structural, and compositional properties was scrutinized by physical and chemical characterizations. The post-annealed RexOy exhibited a high pH sensitivity (57.3 mV pH−1, R2 = 0.99), a lower hysteresis (4.7 mV), and a reduced drift rate (1.7 mV h−1) compared to the as-prepared sample for an analytically acceptable pH range (2–12) along with good stability and reproducibility. The magnified sensing performance originated due to the valence state of Re from Re6+ to Re7+ attributed to each electron transfer for a single H+ ion. The device showed high selectivity for H+ ions, which was confirmed by the interference study with other relevant ions. The feasibility of the sensor was verified by measuring the device in real samples. Hence, the ease-of-fabrication and notable sensing performance of the proposed sensor endorsed its implementation for diagnosing pH-related diseases.