Two-dimensional nanosheets of semiconductor metal oxides are considered as promising for use in gas sensors, because of the combination of a large surface-area, high thermal stability and high sensitivity, due to the chemisorption mechanism of gas detection. In this work, 2D SnO2 nanosheets were synthesized via the oxidation of template SnS2 nanosheets obtained by surfactant-assisted one-pot solution synthesis. The 2D SnO2 was characterized using transmission and scanning electron microscopy (TEM, SEM), X-ray diffraction (XRD), low-temperature nitrogen adsorption, X-ray photoelectron spectroscopy (XPS) and IR spectroscopy. The sensor characteristics were studied when detecting model gases CO and NH3 in dry (RH25 = 0%) and humid (RH25 = 30%) air. The combination of high specific-surface-area and increased surface acidity caused by the presence of residual sulfate anions provides a high 2D SnO2 sensor’s signal towards NH3 at a low temperature of 200 °C in dry air, but at the same time causes an inversion of the sensor response when detecting NH3 in a humid atmosphere. To reveal the processes responsible for sensor-response inversion, the interaction of 2D SnO2 with ammonia was investigated using diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) in dry and humid air at temperatures corresponding to the maximum “positive” and maximum “negative” sensor response.