A staunch member of Jefferson's Democratic-Republican Party, he led Baltimore during the War of 1812 and was instrumental in organizing the civilian defense of the city.

A bonfire was lit on Gallows Hill, and "to give its flame a brighter glow", six large casks of imported gin from Holland (on which England had exacted tax) were thrown onto it.

Shortly after the outbreak of the war and despite his strong anti-British sentiments and anti-Federalist political views, he was nearly killed unsuccessfully trying to stop a mob who had stormed the Baltimore City Jail intent on lynching Alexander Hanson, the publisher of an extreme Federalist newspaper, and his allies who included Henry "Light-Horse Harry" Lee.

It was during this period that Johnson guided the city through a serious epidemic of yellow fever and commissioned a report on the possible causes of the outbreak from the physicians who had attended the victims.

During the course of his career, Johnson also served as a judge of the County Court,[10] a trustee of St. Peter's School (a home for orphan boys),[11] and a director of the Bank of Baltimore.

[13]The house where Edward and Elizabeth Johnson lived on East Lombard Street, not far from the site of the brewery he once owned, is still standing and bears a commemorative plaque as does a tree dedicated to him at Fort McHenry National Monument and Historic Shrine.