Single breath-hold 3D-UTE-MRI was proposed for simultaneous evaluation of lung morphology and function. Sixteen patients with cystic fibrosis (CF) underwent initial and follow-up 3D-UTE-MRI in 2019 and 2021. In line with a previous study, referenced voxelwise fractional ventilation (FV) provided a marker that correlates strongly with the lung clearance index (LCI), reflecting ventilation inhomogeneity. Seven patients received a new drug-combination (ivacaftor/elexacaftor/tezacaftor) with significantly improved lung function during clinical follow-up. Similarly, significantly decreased ventilation inhomogeneity was derived from functional MRI. Thus, single breath-hold 3D-UTE MRI is a valuable tool for monitoring ventilation inhomogeneity in patients with CF during drug treatment.