A new synthetic entry to iridium Keggin-type polyoxometalate complexes from [PW11O39]7– and K3[IrCl6] under harsh conditions is reported. The complex [PW11O39IrCl]5– (15–) featuring an IrCl functionality was obtained in high yield and characterized by NMR spectroscopic and ESI-MS techniques. The presence of Li+ (3–4 M) is essential for a quantitative yield of 15–. The reactivities of 15– and its rhodium analogue [PW11O39RhCl]5– in ligand substitution at the noble metal site were studied. Thiocyanate coordination successfully yielded (Bu4N)5[PW11O39M(SCN)] [M = Rh (2a), Ir, (3a)]. In both cases, the SCN ligands are coordinated by sulfur atoms, according to 13C NMR and IR spectroscopic data. Gas-phase fragmentation reactions of compounds 2a and 3a were also investigated by collision-induced dissociation (CID) experiments. Reaction of [PW11O39RhCl]5– with NaN3 resulted in Cl– to OH– replacement accompanied by the liberation of the RhCl fragment, whereas 15– proved unreactive with NaN3. Attempts to coordinate NO2– are adversely affected by competing noble metal excision with formation of free [PW11O39]7–.