||Bis(2-phenylpyridine)(acetylacetonate)iridium, Ir(ppy)2(acac), is a benchmark green emitter for phosphorescent organic light-emitting diodes (PhOLEDs). In this work, we reported three positional isomeric cyano-substituted Ir(ppy)2(acac) complexes, i.e., Ir(3-CN), Ir(4-CN), and Ir(10-CN), with the emission in the yellow to red region (544–625 nm). Through theoretical investigation and single-crystal analysis, it was found that the introduction of cyano substitution at various positions of the ppy ligand allows for tuning the electron distribution and coordination bond length of Ir complexes. Therefore, the charge transfer property of Ir complexes is enhanced such that the energy gap of the cyano-substituted Ir(ppy)2(acac) complexes was reduced. In addition, Ir(3-CN), Ir(4-CN), and Ir(10-CN) exhibited high PLQYs of 83, 54, and 75%, respectively, with the phosphorescence lifetime in the range of 0.79–2.08 μs. Notably, the device utilizing Ir(3-CN) as the emitter exhibited a maximum external quantum efficiency (EQE) of 25.4%, current efficiency of 56.9 cd A–1, power efficiency of 68.7 lm W–1, and brightness of 61,340 cd m–2 at 8 V. The EQE of this device remained 24.3 and 19.9% at luminances of 1,000 and 10,000 cd m–2, corresponding to the efficiency roll-off of 4.3 and 21.7%, respectively. Comparing to the Ir complexes using the ligand with an extended conjugated structure, our results demonstrated a simple molecular design strategy for phosphorescence emitters with reduced molecular weight for efficient PhOLEDs in the yellow to red color region.