Abstract Purpose This study aimed to (1) document patterns of quadriceps muscle wasting in the first 10 days of admission and (2) determine the relationship between muscle ultrasonography and volitional measures. Materials and methods Twenty-two adults ventilated for more than 48 hours were included. Sequential quadriceps ultrasound images were obtained over the first 10 days and at awakening and intensive care unit (ICU) discharge. Muscle strength and function were assessed at awakening and ICU discharge. Results A total of 416 images were analyzed. There was a 30% reduction in vastus intermedius (VI) thickness, rectus femoris (RF) thickness, and cross-sectional area within 10 days of admission. Muscle echogenicity scores increased for both RF and VI muscles by + 12.7% and + 25.5%, respectively (suggesting deterioration in muscle quality). There was a strong association between function and VI thickness ( r = 0.82) and echogenicity ( r = − 0.77). There was a moderate association between function and RF cross-sectional area ( r = 0.71). Conclusions Muscle wasting occurs rapidly in the ICU setting. Ultrasonography is a useful surrogate measure for identifying future impairment. Vastus intermedius may be an important muscle to monitor in the future because it demonstrated the greatest change in muscle quality and had the strongest relationship to volitional measures.