The results were well in line with those suggested by polls and observers, who cited Layton's personal popularity and the riding's deep NDP roots.
NDP candidate Craig Scott, a law professor, human rights lawyer and neophyte politician, emerged on top with the kind of voting numbers Layton enjoyed.
Scott conceded that Layton had played "a huge role" in his win.
"He was a huge part of building this party, nationally and in this riding," Scott said.
"So, I stood on the shoulders of giants and Jack was one of those giants — the biggest of all, if you like."
Voters, Scott said, had rejected the politics of division represented by the Conservatives under Prime Minister Stephen Harper.
Layton's widow, MP Olivia Chow, was ecstatic at the result.
"It means the NDP 'orange wave' is continuing and the people in Toronto-Danforth are proud to have a member of Parliament to stand up to Stephen Harper and get their voice heard," Chow said in an interview.
"I am sure Jack would have been proud of Craig Scott as a member of Parliament."
The Liberal candidate, ad executive Grant Gordon, came in a distant second with about 29 per cent of the votes cast.
"I wish you all the best of luck in Ottawa," Gordon said in his concession speech. "Alas . . . you do have to go to Ottawa."
The Conservatives' Andrew Keyes, who kept a low profile during the campaign, garnered around five per cent of the vote, just ahead of the Greens' Adriana Mugnatto-Hamu.
Roughly 43 per cent of the 74,500 eligible voters actually cast ballots, Elections Canada reported, down from 64.9 per cent in the general election last year.
While the win boosts the NDP standing in the Commons to 102 seats, observers said the results would have little impact on the wider political scene.
The Conservatives remain in the majority with 165 seats, the Liberals have 35, the Bloc Quebecois four seats, the Green Party one, and there's one independent.
Toronto-Danforth, just to the east of the city's downtown area, is a diverse riding, with large Greek, Chinese and other ethnic communities.
Layton, who died last August, claimed the riding from the Liberals in 2004 in a close race, but his popularity increased in the following years. In his last ballot last year, he took just over 60 per cent of the vote.
Observers said Layton's personal popularity along with the riding's roots helped keep the riding firmly in NDP hands.
Chow said no one can fill the shoes of another, but she called Scott a "principled and smart" man who "shared the same values" and would stay true to Layton's vision.
Gordon, whose campaign began late, had the help of Liberal heavyweight, interim party leader Bob Rae, who once held the riding as a New Democrat, and MP Justin Trudeau, but their presence had little impact.
"We all knew from the outset that there were going to be profound feelings of loyalty to Mr. Layton," Rae said.
On the weekend, the NDP holds a convention to choose a national leader to replace Layton.
All the leadership candidates were on hand for Scott's win at a hall in the riding.
Outgoing interim NDP leader Nicole Turmel said Layton had stood up for families in the riding.
"Starting tonight, Craig will pick up where Jack left off," Turmel said.
"Craig has spent his life fighting for people and will serve Toronto-Danforth with passion and dedication."
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