A novel isoreticular oxamato-based manganese(II)–copper(II) open metal–organic framework H2O@iso1 featuring a pillared square/octagonal layer structure with alternating open and closed octagonal pores has been rationally prepared. The open-framework topology is responsible for a large selectivity in the separation of small gas (CO2 over CH4) and vapor molecules (CH3OH over CH3CN and CH3CH2OH). H2O@iso1 displays a long-range three-dimensional ferromagnetic ordering with a drastic variation of the critical temperature as a function of the guest molecule [TC < 2.0 K (CO2@iso1 and CH4@iso1) and TC = 6.5 (CH3OH@iso1) and 21.0 K (H2O@iso1)].