Ferric ion (Fe³⁺) is a biologically abundant and important metal ion. We developed several cyclometalated iridium complex-based molecular sensors (1, ppy-1, 1-phen, 1?a, and 1_OMe) for the detection of Fe³⁺ using an acetal moiety as the reaction site. The acetal moiety in iridium complexes undergoes Fe³⁺-catalyzed hydrolysis and subsequent formation of a formyl group, resulting in turn-off photoluminescent and electrochemiluminescent responses. Sensor 1 showed excellent selectivity toward Fe³⁺ over other biologically important metal ions. Furthermore, we compared the performance of the sensors based on the structural differences of the iridium complexes, and revealed a relationship between the structure and chemical properties through electrochemical experiments and computational calculations.