The coordination of actinides and lanthanides, as well as strontium and cesium with graphdiyne (GDY) was studied experimentally and theoretically. On the basis of experimental results and/or theoretical calculations, it was suggested that Th4+, Pu4+, Am3+, Cm3+, and Cs+ exist in single‐ion states on the special triangular structure of GDY with various coordination patterns, wherein GDY itself is deformed in different ways. Both experiment and theoretical calculations strongly indicate that UO22+, La3+, Eu3+, Tm3+ and Sr2+ are not adsorbed by GDY at all. The distinguished adsorption behaviors of GDY afford an important strategy for highly selective separation of actinides and lanthanides, Th4+ and UO22+, and Cs+ and Sr2+, in the nuclear fuel cycle. Also, the present work sheds light on an approach to explore the unique functions and physicochemical properties of actinides in single‐ion states.