This work presents the first in-depth analysis of the ionospheric response to a large-scale lava fountain that occurred at Mt.Etna (Italy) on December 4th, 2015. Thanks to the extensive monitoring and surveillance system around Mt. Etna, we are able to conduct a multi-data study to investigate the ionospheric response during the volcanic activity. We analyze the timing of the eruption and of the plume convection using seismo-acoustic data and videos in visible and thermal channels. We also analyze Global Navigation Satellite Systems (GNSS) observations to investigate the induced ionospheric perturbation in total electron content (TEC) estimates, using the VARION algorithm. Our analysis reveals localized TEC signatures extending from above the volcano summit up to approximately 200 km south/south-west of the volcanic vent. The ionospheric perturbation is a quasi-periodic signal lasting around 30 - 45 minutes with period ranging basically between 15 - 25 minutes, peak-to-peak amplitude around 1.2 TECU (vertical component) and an horizontal apparent wave velocity varying between 135 - 300 m/s with spectral peak frequency between 0.5 - 1.5 mHz. We also compare the outputs from the Fast Fourier Transform with those from Empirical Mode Decomposition technique to confirm the presence of the perturbation and individualize its onset time in the ionosphere. The arrival time in the ionosphere is around 20 minutes starting from the seismo-acoustic onset of the eruption. Finally, the extremely dense and local GNSS network enabled, for the first time, the detection of acoustic-gravity wave induced ionospheric perturbation forced by Mt. Etna.