The blaze was reported at 7:30 p.m and fire department spokesman Mark Messier said shortly after that the blaze was confined to the attic.
He said the British high commissioner, his wife and two other adults were outside the building when crews arrived.
There was substantial damage to the interior of the building and crews moved paintings, artifacts and other contents to protect them from the fire. Furniture and other items in the home were also covered to protect them from water and smoke.
Damage has been estimated at $250,000, said Messier.
Foreign Affairs Minister John Baird was returning to his office across the road from the residence and stopped when he saw the fire trucks.
He was allowed past the yellow security tape and into the mansion to meet with the envoy.
"This is a really important building for Canadian history," Baird told reporters later.
"We're thrilled and very thankful that no one has been injured."
High Commissioner Andrew Pocock also talked with people outside the building.
The Victorian manor at 140 Sussex Dr. has been the official residence of the British High Commissioner since 1930. It is one of Canada's most prestigious addresses and Prime Minister Stephen Harper and the French ambassador are neighbours.
It was built in 1857 and was Macdonald's home from 1883 to 1891.
Former British high commissioner Anthony Carey was among a long line of British envoys who delighted in taking visitors on a tour of the elegant greystone mansion perched on a spectacular plot of land overlooking the Ottawa River.
The cause of the fire remains under investigation and the office of the Fire Marshal and the Ottawa police arson unit will also be assisting with the investigation.