The presence of macrozones (or micro-textured regions) in Ti-6Al-4V (Ti-64) was shown to be a potential cause to the onset of cold dwell fatigue which reduces fatigue life significantly. Past research has demonstrated the potential of using ultrasonic testing for macrozone characterization, with the variation of ultrasound attenuation, backscatter and velocity in the presence of macrozones. However, due to the complexity of the microstructure, some physical phenomena that were observed are still not well understood. In this study, we propose the use of finite-element polycrystalline models to provide us with a means to systematically study the wave-macrozone interaction. Through this investigation performed using two-dimensional models, we are able to identify important correlations between macrozone characteristics (size, shape and texture) and ultrasound responses (attenuation, backscatter and velocity). The observed behaviours are then validated experimentally, and we also highlight how this understanding can potentially aid with the characterization of macrozones in Ti-64 samples.