Abstract We propose a method of measuring the transient diffusion of vapor mixtures through flat dense membranes. The experimental setup consists of a self-developed differential permeation cell and a real-time analyzer to monitor the permeate–sweep gas mixture. The selectivity and the low sampling period of the real-time analysis are ensured by combining a quadrupole mass spectrometer and a gas chromatograph equipped with an inert capillary column. The proposed method is demonstrated at 298 K on the following binary mixtures of vapors: p-xylene–octane and toluene–octane permeating through low density polyethylene, and propan-1-ol–butan-1-ol vapors permeating through polydimethylsiloxane and through polydimethylsiloxane filled with montmorillonite. Based on extended Fick’s laws, we evaluate parameters describing cross-diffusion effects, using the Gauss–Newton method and finite difference modeling. In contrast to the transient diffusion of pure compounds, the simultaneous diffusion of a binary mixture of vapors is influenced by the dynamics of each diffusing compound. The effect on the transient diffusion of each vapor can be either positive or negative, depending on the type of membrane and on the actual mixture of vapors. Moreover, this cross-effect is mitigated by the presence of a filler, specifically of montmorillonite in polydimethylsiloxane in this particular case.