Isothermal vapor–liquid equilibrium (VLE) data for the oxygen or nitrogen with perfluorobutane (R610) systems are presented. The measurements were performed at three temperatures (293, 313, and 333) K and pressures up to 17.014 MPa using a static-analytic apparatus fitted with a rapid online sampler injector, a reliable tool for sampling equilibrium phases. The measurement uncertainties were within 0.04 K for temperature, 0.008 MPa for pressure, and 0.04 for mole fractions. The experimental VLE data for both systems were successfully modeled using the direct method and adjusted through the flash calculation objective function. The modeling approach combined the Peng–Robinson equation of state with the Mathias–Copeman alpha function and the Wong-Sandler mixing rule utilizing the nonrandom two-liquid activity coefficient model.