Infrasound signals are used to investigate and monitor active volcanoes during eruptive and degassing activity. Infrasound amplitude information has been used to estimate eruptive parameters such as plume height, magma discharge rate, and lava fountain height. Active volcanoes are characterized by pronounced topography and, during eruptive activity, the topography can change rapidly, affecting the observed infrasound amplitudes. While the interaction of infrasonic signals with topography has been widely investigated over the past decade, there has been limited work on the impact of changing topography on the infrasonic amplitudes. In this work, the infrasonic signals accompanying 57 lava fountain paroxysms at Mt. Etna (Italy) during 2021 were analyzed. In particular, the temporal and spatial variations of the infrasound amplitudes were investigated. During 2021, significant changes in the topography around the most active crater (the South East Crater) took place and were reconstructed in detail using high resolution imagery from unoccupied aerial system surveys. Through analysis of the observed infrasound signals and numerical simulations of the acoustic wavefield, we demonstrate that the observed spatial and temporal variation in the infrasound signal amplitudes can largely be explained by the combined effects of changes in the location of the acoustic source and changes in the near-vent topography, together with source acoustic amplitude variations. This work demonstrates the importance of accurate source locations and high-resolution topographic information, particularly in the near-vent region where the topography is most likely to change rapidly and illustrates that changing topography should be considered when interpreting local infrasound observations over long time scales.