A photothermal deflection (PD) technique was applied to measure the binary diffusion coefficients of various gases (CO2–N2, CO2–O2, N2–He, O2–He, and CO2–He). With an in-house-made Loschmidt diffusion cell, a transverse PD system was employed to measure the time-resolved PD signal associated with the variation of the thermal diffusivity and the temperature coefficient of the refractive index of the gas mixture during the diffusion. The concentration evolution of the gas mixture was deduced from the PD amplitude and phase signals based on our diffraction PD model and was processed using two mass-diffusion models explored in this work for both short- and long-time diffusions to find the diffusion coefficient. An optical fiber oxygen sensor was also used to measure the concentration changes of the mixtures with oxygen. Experimental results demonstrated that the binary diffusion coefficients precisely measured with the PD technique were in agreement with the literature values. Moreover, the PD technique can measure the diffusion coefficients of various gas mixtures with both short- and long-time diffusions. In contrast, the oxygen sensor is only suitable for the long-time diffusion measurements of the gas mixtures with oxygen.