Io is one of Jupiter’s largest moons and the most volcanically active body in the Solar system. Its very active surface has hotspots produced by volcanic eruptions popping up at seemingly random locations and times. Characterizing the complex surface of Io requires the highest angular resolution available. This work presents the analysis of aperture masking interferometric observations (at 4.3 μm) of Io taken with the Near-Infrared Imager and Slitless Spectrograph instrument on the James Webb Space Telescope. These are the first space-based infrared interferometric observations of a Solar system body ever taken. For complex extended objects like Io, the traditional visibility extraction algorithms from interferograms suffer from limitations. Here, new deconvolution methods based on neural networks allowed us to obtain reliable images from which a detailed analysis of the volcanically active surface of this moon was performed. Our study characterizes the loci and brightness of several unresolved volcanoes on the surface of Io, as well as the extended emission observed. We identified the brightest eruption (I4.3μm = 33 ± 4.3 GW μm−1), referred to as V1, within an area to the north–east of Seth Patera (129.4 ± 0.8◦ W. Longitude, 1.5 ± 0.7◦ S. Latitude). Its projected speed (VT = 86 ± 34 m s−1) is consistent with the rotational speed of Io. Additionally, six fainter volcanoes were identified and characterized. Complementary ground-based images, taken with the Keck II telescope, allowed us to benchmark the deconvolved aperture masking interferometric images, showing consistency. Finally, we highlight the importance of characterizing Io’s surface with long-term monitoring at high angular resolution.