A method of manufacturing synthesis gas by catalytic partial oxidation can prevent formation of hot spots from taking place when driving mixture gas to pass through a catalyst-filled layer at high velocity. The method comprises converting mixture gas of source gas containing lower hydrocarbons and oxidative gas containing oxygen into synthesis gas containing hydrogen and carbon monoxide as main components thereof by causing mixture gas to flow through a fixed bed catalyst layer arranged in a reactor. The method of manufacturing synthesis gas by catalytic partial oxidation is conducted such that the mixture gas is made to flow to the catalyst layer under the condition that the Reynolds number does not exceed 20 at the inlet of the catalyst layer.