The Hunga Tonga-Hunga Ha’apai volcano (Pacific Ocean) generated a cataclysmic explosion on 15 January 2022, triggering several atmospheric disturbances at a global scale, as a huge increase in the total electron content (TEC) in the ionosphere, and a pressure wave travelling in the troposphere. We collected and analysed data over the Mediterranean to study these disturbances, and in particular, (i) data from the barometric and infrasonic stations installed on Italian active volcanoes by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) for investigating the tropospheric pressure waves; (ii) barometric data from the INGV-TROPOMAG and SIAS (Sicilian Agro-meteorological Information System) networks, for investigating the interaction between the orography and pressure waves; (iii) ionograms from the Advanced Ionospheric Sounder-INGV ionosonde at Gibilmanna (Sicily, Italy); (iv) data from the RING (Rete Italiana Integrata GNSS) network, to retrieve the ionospheric TEC; (v) soil CO2 flux data from the INGV surveillance network of Vulcano Island. The analysis of the ground-level barometric data highlights that pressure waves were reflected and diffracted by the topographic surface, creating a complex space–time dynamic of the atmospheric disturbances travelling over Sicily, driven by the interference among the different wavefronts. The ionograms show that a medium-scale travelling ionospheric disturbance (MSTID), with a horizontal wavelength of about 220 km and a period of about 35 min, propagated through the ionospheric plasma in the correspondence of the first barometric variations. Moreover, comparing detrended TEC and barometric data, we further confirmed the presence of the aforementioned MSTID together with its close relation to the tropospheric disturbance.