A photoacoustic (PA) cell was designed based on the numerical simulation and then was fabricated in order to investigate the effect of various buffer gases on the acoustic signals and the resonant frequencies. The sizes of resonator and buffer chambers were suitably selected to improve signal-to-noise ratio. Atmospheric SF6 impact is high due to its significant green house effect. A series of experiments were performed to detect SF6 trace in the air and various types of rare gases. Similar experiments were carried out for the urban and industrial pollutant SO2 in the same environments. The resonant frequencies were measured at various pressures for several rare gases, namely He, Ne, Ar, Kr, and Xe. The PA spectroscopy of molecular traces in various gases gives rise to sensible spectral shift. It was shown that the use of heavier buffer gases at atmospheric pressure lead to detection of the lower concentrations. In general, the relatively intense acoustic signal is recorded for the heaviest species Xe due to its large vibrational–transitional excitation cross section. Conversely, the light elements dissipate laser energy much larger than the heavy species during the successive collisional excitations. Therefore the trace molecules in helium exhibit a notable rise in the resonant frequency accompanying a small PA signal.