Aggressive corrosion can occur when firing waste or bio-based fuels, due to the presence of high concentrations of heavy metals, alkali metals, and chlorides. These deleterious compounds deposit on furnace walls and can form mixtures that can rapidly accelerate corrosion. The effect of salts containing lead had not been studied extensively at temperatures lower than 400 °C in nickel-based materials. This study investigates the effect of the individual salts PbCl2 and KCl and their mixture on the high temperature corrosion of alloy 625 at 340 °C and 380 °C. Samples of alloy 625 were covered with individual salts or a salt mixture and exposed to high temperatures in an atmosphere of synthetic air, 20-vol% H2O, and 100 ppm HCl. The results show that the presence of individual salts does not induce observable corrosion attack on alloy 625 after 168 h at any tested temperature. The salt mixture did cause a severe corrosion attack at 380 °C, observed after 24 h of exposure. It is suggested that the salt mixture induces the formation of lead chromates that may prevent or disrupt the formation of a protective chromia scale. It is believed that a key part of the mechanism is the formation of eutectic melts by the interaction of the scale with the salt mixture. Thermodynamic equilibria calculations show that the first melting temperature of PbCl2 and KCl salt mixture after reaction with oxygen can be as low as about 382 °C, and even lower (357 °C) if chromates are present.