The original 1795 house at 28 Prideaux Street was burned by American troops in 1813 during the War of 1812. It was built around 1795 by James Muirhead, a skilled army surgeon and magistrate in the town. Muirhead is acknowledged as the "pioneer doctor" of Niagara.

The lots on Prideaux were considered the most desirable and were allocated by lottery. Muirhead was a surgeon with the Scottish 16th Rifles and came to Niagara in 1790. In 1792 he signed an address of welcome to Lieutenant Governor John Graves Simcoe. He married Deborah Butler, the only daughter of the renowned Colonel John Butler, at St. Mark's Church in 1795. It is known that Muirhead's original house included what was probably the town's first "Apothecary Shop".

At that time the town's Courthouse was across the street from 28 Prideaux and as magistrate, Muirhead would cross the street to hear disputes. As a doctor, Muirhead was one of the first to offer smallpox inoculations and he administered these free to the poor. He ran the field hospital during the War of 1812 where General Brock was taken when fatally shot. Muirhead was a pallbearer in Brock's funeral procession. In June of 1813 Muirhead was marched to Albany, New York as a non-combatant prisoner of war. The march took 57 days.

Muirhead was released at the end of 1813 and returned to Niagara and rebuilt on the site of his original home, probably before 1817. This is the house that stands today. A massive stone wall in the basement along with stone footings survive from the original 1795 home as probably do charred hand hewn beams which are re-used throughout the 1817 house.

In 1822, James Muirhead was appointed Surgeon General. Muirhead died in 1834 and both James' and his son's (Butler Muirhead) tombstones are still visible in Butler's Burying Ground at the extreme south end of Butler Street in town.

28 Prideaux Street is also the only home in Niagara-on-the-Lake to be owned by a Chief Justice of the Supreme Court of Canada, Sir William Buell Richards. Sir William married Deborah Catherine Muirhead (only granddaughter of James and Deborah) in 1846. It was at this time that the rear addition was made to the 1817 house.