Cretan lyra is a stringed instrument very popular on the island of Crete, Greece and an important part of its musical tradition. For stringed musical instruments, the air mode resonance plays a vital part in their sound, especially in the low frequency range. For this study, the air mode resonance of a Cretan lyra is investigated with the use of finite element method (FEM). Two different FEM acoustic models were utilized: first, a pressure acoustics model with the Cretan lyra body treated as rigid was used to provide an approximate result; secondly, an acoustic-structure interaction model was applied for a more accurate representation. In addition, acoustic measurements were performed to identify the air mode resonance frequency. Results of this study reveal that the acoustic-structure interaction model has a 3.7% difference regarding the actual measurements of the resonance frequency. In contrast, the pressure acoustics solution is approximately 13.8% too high compared with the actual measurements. Taken together, findings of this study support the idea that utilizing FEM acoustic-structure interaction models could possibly predict more accurately the vibroacoustic behavior of musical instruments, which in turn can enable the determination of key aspects that can be used to control the instrument’s tone and sound quality.