Mulcair says the Tories have for years lauded Rob Ford, who the NDP leader called their ideological "poster child."
But Mulcair says the association has now tainted the Conservatives following months of revelations about the mayor's behaviour that includes admitted drug use.
Mulcair says the long-standing Tory-Ford ties are souring voters' opinion of Harper, and will play a role in the 2015 federal election.
Harper and Ford have had a cosy relationship over the years, culminating with the pair enjoying a fishing trip together at Harrington Lake, Que., shortly after the Tories won re-election in 2011.
The prime minister later attended a barbecue hosted by Ford and praised the mayor.
"The Conservatives have been saying for years that Rob Ford's their guy," Mulcair said Sunday during a surprise stop in Toronto to support his party's candidate in the coming federal byelection.
"They're going to have to wear it now," he said, repeating that Ford should resign immediately and get help.
Natural Resources Minister Joe Oliver sought to distance his government when asked about the mayor earlier this month, denying there was any particularly close relationship.
Finance Minister Jim Flaherty — a Ford family friend who has appeared with the mayor at several events — became visibly upset this month when commenting on Ford's troubles, but said he has to make his own decision on what to do.
Liberal Leader Justin Trudeau has said he hopes Ford seeks treatment for his demons.
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