Ford, who is running for re-election as mayor of Canada's largest city, said on Tuesday he would attend this meeting to make sure that Toronto gets its "fair share" of a new federal infrastructure plan.
Vancouver Mayor Gregor Robertson, as chair of the group, will speak to reporters in Ottawa after the mayors' morning session.
CBCNews.ca will carry the news conference live starting at 11:30 a.m. ET.
Wednesday's meeting will also mark the first time former Liberal MP Denis Coderre will meet his municipal counterparts since being elected Montreal mayor.
Calgary Mayor Naheed Nenshi told CBC News on Monday the mayors are expected to spend a "fair bit of time" discussing the growing housing crisis with Candice Bergen, the federal minister of state for social development.
"I'm looking forward to that discussion and continuing that discussion with the federal government about the housing crisis that we're facing across municipalities in Canada," Nenshi said in Calgary Monday.
The federal government's key infrastructure plan will also be a main topic of discussion as numerous questions remain on how the federal funds will be used to meet municipal needs.
"There were some concerns that we had with the criteria of the Building Canada Fund. As I've said before, I think these are solvable… and if they're not solvable for 2014, let's at least fix them for 2015," Nenshi said.
The federal government recently announced the details of a 10-year, $14-billion New Building Canada Fund designed to provide both small and large communities with predictable infrastructure funding.
Of that $14 billion fund, $10 billion has been earmarked to fund provincial and territorial infrastructure projects.
Under the new plan, each province and territory will receive a base funding amount of $250 million per year, plus a per capita amount based on the 2011 census figures.
As it is, Ontario will receive $2.7 billion over 10 years from Ottawa, the most federal dollars of any province. Quebec will receive $1.7 billion and British Columbia just over $1 billion over 10 years under the new plan.
Glen Murray, Ontario's minister of infrastructure, was critical of the new plan and called on the federal government to commit more money to infrastructure spending.
"Since they collect the majority of taxes, we need them as a full partner. The Building Canada Fund might do many things, but it doesn't do much building in Canada," Murray told reporters in Toronto on Tuesday.
$660M for Toronto subway
How the federal dollars will be allocated is the question on the mind of anyone who intends to apply for funding under the new federal infrastructure plan.
Ford said on Tuesday that "years of under-investment" have left Toronto far behind where the city ought to be when it comes to transit and housing needs.
While cities can't apply for the new federal dollars until March 31, Prime Minister Stephen Harper announced last fall that Toronto would receive $660 million for the extension of a subway line.
"This vital project will drive economic development and unlock countless opportunities," Ford said in Toronto on Tuesday.
"This is a great first step and a major achievement. But even with the Scarborough subway line, our transit system is still years behind where it needs to be."
"The city of Toronto faces unique challenges and we need the federal government to acknowledge this," Ford said.
Ford, who is a longtime friend of federal Finance Minister Jim Flaherty, will not be meeting with him while in Ottawa. Nor will the mayor be meeting with Harper, the Prime Minister's Office told CBC News on Tuesday.
Federal Conservatives have tried to steer clear of answering questions about the embattled mayor's use of alcohol and drugs, with the exception of cabinet minister Jason Kenney, who said Ford should "step aside."
Kenney may have rubbed Flaherty the wrong way with his comments, but he was seen as representing the concerns of his caucus colleagues at the time.
The Big City Mayors' Caucus consists of 22 mayors who are members of the Federation of Canadian Municipalities, a group that represents more than 2,000 communities across the country.