The objective is to understand the differences in the lesion formation processes between microwave and high-intensity focused ultrasound (HIFU) ablation. The lesions formed by microwaves and HIFU were real-time monitored and compared using transparent tissue-mimicking phantoms at 60 and 70 W of driving electrical power. Microwaves and HIFU produced lesions different in shape, size, and developing processes. For HIFU ablations, the hyperechoic region appeared bigger in ultrasonic images, as compared with the protein denatured region observed optically at the end of 100 s ablations. On the contrary, the hyperechoic signal was only limited to a small region along the antenna of a microwave ablator. Careful monitoring and controlling the lesion formation process is essential for successful microwaves and HIFU thermal ablations.