A protein‐sized (ca. 4.2×4.2×3.6 nm3) non‐biologically derived molecule {Nb288O768(OH)48(CO3)12} (Nb288) containing up to 288 niobium atoms has been obtained, which is by far the largest and the highest nuclearity polyoxoniobate (PONb). Particularly, in terms of metal nuclearity number, Nb288 is the second largest cluster so far reported in classic polyoxometalate chemistry (V, Mo, W, Nb, and Ta). Nb288 can be described as a giant windmill‐like cluster aggregate of six nanoscale high‐nuclearity PONb units {Nb47O128(OH)6(CO3)2} (Nb47) joined together by six additional Nb ions. Interestingly, the 47‐nuclearity Nb47 units generated in situ can be isolated and bridged by copper complexes to form an inorganic–organic hybrid three‐dimensional PONb framework, which exhibits effective catalytic activity for hydrolyzing nerve agent simulant of dimethyl methylphosphonate. The unique Nb47 cluster also provides a new type of topology to very limited family of Nb‐O clusters. Riesengroß ist ein Polyoxoniobat (PONb) mit 288 Nb‐Zentren – das mit Abstand größte PONb und das Polyoxometallat mit der zweithöchsten Zahl an Metallatomen. Das PONb enthält eine in situ gebildete 47‐kernige Baueinheit, die durch Metallkomplexe unter Bildung eines ausgedehnten PONb‐Gerüsts stabilisiert werden kann und in der Lage ist, Dimethylmethylphosphonat zu hydrolysieren.