A novel mid-infrared hollow waveguide gas sensor was developed to target H218O, H216O, H217O, and HDO absorption lines at 3662.9196, 3663.04522, 3663.32128, and 3663.84202 cm−1, respectively, based on wavelength modulation spectroscopy using a 2.73 µm distributed feedback diode laser. A hollow waveguide fiber with a 5-m length and 1-mm inner diameter was used for gas absorption. A dew point generator with liquid water with known water–isotope ratios was used to calibrate the sensor. Detection limits of 35.18 ppbv, 4.69 ppmv, 60.53 ppbv, and 3.88 ppbv were obtained for H218O, H216O, H217O, and HDO, respectively, in a 96-s integration time, which resulted in isotopic ratio measurement precision of 0.85‰, 0.57‰, and 10.48‰ for δ18O, δ17O, and δD, respectively. Field measurements of H218O, H216O, and H217O concentration were conducted on the Nanchang Hangkong University campus to evaluate sensor performance.