The invention discloses a comprehensive treatment device and method for cooling desulfurization of a high-temperature and high-humidity flue gas. The device comprises a heat exchanger connected with the outlet of high-temperature flue, an inertia separator connected with the heat flow outlet of the heat exchanger, a cooling and dedusting flue connected with the outlet of the inertia separator, a steam-water separator connected with the outlet of the cooling and dedusting flue, and a wet-type desulfurization tower connected with the outlet of the steam-water separator, wherein the cooling and dedusting flue is arranged slantly; the inlet end of the cooling and dedusting flue is positioned below the outlet end of the cooling and dedusting flue; a plurality of layers of spraying devices are arranged in the cooling and dedusting flue; and the flue gas outlet of the wet-type desulfurization tower is connected to the cold flow inlet of the heat exchanger. Aiming at the characteristics of high temperature, low flue gas purification temperature and the like of the high-temperature and high-humidity flue gas, the comprehensive cooling desulfurization treatment is carried out on the high-temperature and high-humidity flue gas by combination of the heat exchanger with a repeated straight-cold cooling mode under the condition that the flue gas temperature at a wet-type desulfurization inlet is controlled within 80 DEG C to 100 DEG C, so that the high desulfurization efficiency is ensured. The device is simple and low in cost.