Major (Si, Al, Fe, Ti, Ca, Mg, Na, K, and S) and trace (Ag, As, B, Ba, Be, Bi, Br, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Ga, Gd, Ge, Hf, Ho, I, La, Li, Lu, Mn, Mo, Nb, Nd, Ni, Pb, Pr, Rb, Sb, Sc, Se, Sm, Sn, Sr, Ta, Tb, Th, Tl, Tm, U, V, W, Y, Yb, Zn, and Zr) elements were determined in experimental leachates of fly ash from the Ptolemais coal-fired power plant (Northern Greece). This plant has a total capacity of 620 MW and consumes lignite from the Ptolemais basin. Experimental leaching was carried out using one stage and column leaching procedures. These leaching experiments allowed for the characterization of the relative mass leached and the element behavior in function of time. Relative mass leached is generally low. Only Sr and Mo are lost during the first five pore volumes of the leaching. The foremost transformations are relatively fast, implying mainly Ca and S reactions and an important lowering of pH values. The results can be used in the disposal assessment of this combustion by-product to model more accurately the behavior of major and trace elements released during fly ash landfilling.