This paper presents a monolithic 4×4 tin oxide gas sensor array together with on-chip multiplexing and differential read-out circuitry. In contrast to the conventional voltage divider read-out technique, a novel differential read-out circuit (DRC) for tin oxide gas sensors is proposed. The output of the DRC is simply proportional to the difference between the voltage on the two electrodes of the sensor but not to the transistor parameters such as mobility and threshold voltage, neither to the supply voltage. A robust fabrication process focusing on the integration of the CMOS circuitry and the MEMS structures is described. The monolithic sensor array and its processing circuitry have been implemented in our in-house 5 μm process. Experimental results showed good linearity at the output of the DRC for a wide range of sensor resistance variation (over 20 MΩ). Results also show good thermal characteristic leading to only 15.5 mW power consumption for 300°C operating temperature.