Provided are a substrate processing apparatus and a method of manufacturing a semiconductor device. The substrate processing apparatus includes a reaction vessel configured to process a substrate, a heater configured to heat an inside of the reaction vessel, a gas supply line configured to supply gas into the reaction vessel, a first valve installed at the gas supply line, a flow rate controller installed at the gas supply line, a main exhaust line configured to exhaust the inside of the reaction vessel, a second valve installed at the main exhaust line, a slow exhaust line installed at the main exhaust line, a third valve installed at the slow exhaust line, a throttle part installed at the slow exhaust line, a vacuum pump installed at the main exhaust line, and a controller configured to control the valves and the flow rate controller.