Volcanic eruptions can release large amounts of tephra, lava, and gases, drawing attention due to their magnitude, energy, and impact on life and the environment. Among the most documented and sometimes dramatic effects of volcanic ashes are those linked to the input of diverse elements in the environment, which are released as a consequence of ash weathering. Laboratory studies have been conducted to investigate and predict the environmental input of chemical elements from volcanic ashes. This research paper describes the optimization of batch leaching tests used to investigate the release of ions from ashes collected in the Andes Cordillera after the eruption of the Puyehue volcano in 2011. Chemometric multivariate strategies were employed to evaluate the influence of variables affecting the leaching of volcanic ash. The effects of the main variables, namely contact time, the acidity of the leaching agent, the solid/liquid ratio, the particle size, and the stirring speed, were studied in leaching tests. To determine the optimal conditions for selected metal determinations, we employ Darringer's desirability function, which allows for the simultaneous optimization of the selected responses (element concentrations during the leaching process). Multielemental analysis (Na, Mg, Al, Si, P, Cl, K, Ca, V, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Cd, Hg, Tl, and Pb) was quantified by ICP-MS (inductively coupled plasma-mass spectrometry) following adequate dilution of test leaching. These results established the optimal experimental conditions for leaching volcanic ash. The most significant variables were the solid/liquid ratio and the stirring speed, resulting in two groups of elements with an adequate global desirability function (D) value.