Fundamental processes taking place in UV and IR laser ablation and their significance for LA-ICP-MS measurements were investigated with synthetic glassy materials. LA-ICP-MS experiments were conducted on several vitreous and crystallized matrices with different composition using two Nd∶YAG laser ablation systems operating at 1064 nm and 266 nm. Macro-scale effects of the laser factors and matrix properties were evaluated with ICP-MS detection. In-situ investigation of the laser ablation process was carried out at the micro-scale to assess physical and chemical transformations of the original material, based on electron probe microanalysis of ablation products collected on filters and laser impacts. Fragments and beads in the 1–10 µm range enriched in refractory elements (Ca, Al) were characteristic of IR laser ablation, whereas sub-microscopic particles with similar composition to the original matrix were found for UV laser ablation. LA-ICP-MS response factors for matrix and minor elements appeared to be dependent on both the chemical composition and structure of the matrix (up to 30% and 60% for the UV and IR laser, respectively) and were also different for the two lasers by a factor 10. The use of La, a refractory matrix element, as an internal standard could compensate for differences in the ablation yield and thus limit matrix effects. However, fractionation effects were observed for the IR laser and also, to a lesser extent, with the UV one for volatile elements (e.g., Pb, As, B, Cs). Elemental fractionation effects were correlated with the oxide melting point of the elements as the LA-ICP-MS response factors for the IR laser normalized by the UV ones showed a linear relation with this parameter. At the micro-scale, the samples underwent physical and chemical differentiation that could be explained in terms of fusion, vaporization and fragmentation, resulting in the recombination of the analytes in the ablation products.