ABSTRACT One‐step removal of C 2 H 6 /C 3 H 8 and moisture from natural gas can enhance both energy conversion efficiency and transportation safety. However, this remains a significant challenge due to the opposite polarity of C 2 H 6 /C 3 H 8 and H 2 O. Here, one‐step upgrading of wet natural gas can be achieved through integrating amphiphilic sites and adaptive pores in a metal‐organic framework ( FJI‐H36‐Cu ). FJI‐H36‐Cu not only possesses conjugated groups capable of capturing C 2 H 6 /C 3 H 8 and Cu(II) sites that can adsorb H 2 O, but also has a flexible framework that can undergo guest‐driven adaptive transformations (including channel deformation and Cu(II) site reconfiguration) and guest‐regulated controllable thermal expansions (from anisotropy to isotropy). FJI‐H36‐Cu hardly adsorbs CH 4 but can efficiently capture C 2 H 6 /C 3 H 8 , where both C 2 H 6 and C 3 H 8 can simultaneously achieve very high adsorption capacities and very low adsorption enthalpies. Such excellent adsorption performance stems from the adaptive response of FJI‐H36‐Cu to different alkanes; both C 2 H 6 and C 3 H 8 can enhance adsorption by inducing significant deformation, while CH 4 cannot. Moreover, FJI‐H36‐Cu exhibits a high H 2 O adsorption capacity but a very slow adsorption rate, ensuring that the presence of H 2 O does not interfere with C 2 H 6 /C 3 H 8 capture. All these enable FJI‐H36‐Cu to efficiently remove C 3 H 8 , C 2 H 6 , and H 2 O from wet natural gas, achieving very high CH 4 productivity.