Abstract Multi-walled carbon nanotubes (CNTs) and zeolitic imidazole frameworks (ZIF-301) were synergistically incorporated into glassy polysulfone (PSF) to prepare mixed-matrix membranes (MMMs) to separate CO2 from post combustion flue gas. The flexible MMMs rendering consistent distribution and improved adhesion of nanofillers with the polymer matrix were hydrothermally stable under wet conditions. Gas sorption analysis along with dry and wet gas permeation experiments showed that both CO2 permeability and CO2/N2 selectivity of MMMs were improved owing to the synergistic effect of nanofillers. The MMM filled with 18 wt % ZIF-301 nanofillers and 6 wt % CNTs showed an optimum separation performance by providing a CO2 permeability of 19 Barrers with a CO2/N2 selectivity of 48. The CO2 separation performance of MMMs prepared in this work was found to be better than those of already existing hydrothermally stable MMMs.