They'll be chatting about computerized manhole covers, new uses for natural gas and the reading skills of third-graders, among other civic matters. And they'll be hashing out a platform on weighty issues such as the military's involvement in Afghanistan and federal budget cuts.
"Baltimore is front and center, and you're going to hear the word 'Baltimore' for the next four days," said Tom Cochran, the conference's executive director.
Mayor Stephanie Rawlings-Blake described the event as an "incredible opportunity" to show off the city.
"You get more excited when you see [the city] through the eyes of someone who hasn't been here before," she said, adding that she was eager to show how the city's universities and medical institutions are helping Baltimore grow.
Guests will explore art studios in Clipper Mill, attend a party hosted by developer Pat Turner at Silo Point and hear John Waters deliver his one-man show, "This Filthy World."
They'll be playing bocce in Little Italy — appropriate, since House Democratic leader Nancy Pelosi and her big brother, former Baltimore Mayor Thomas J. D'Alesandro III, who grew up in the neighborhood, will be in attendance.
The conference, which will be held in Baltimore for the first time in its 79-year history, could provide a chance for Rawlings-Blake to bring national attention to the city's needs, political experts said.
"She'll be raising the city's profile, and she might also make it more visibile to federal officials who hand out money," said Matthew Crenson, professor emeritus of political science at the Johns Hopkins University.
Donald Norris, chairman of the public policy department at the University of Maryland, Baltimore County, said hosting the conference is a nice addition to Rawlings-Blake's resume, but voters will probably not remember it when they head to the polls for the September Democratic primary in the mayor's race.
"It's a good thing to have, but by itself, it doesn't mean anything," said Norris, adding that Rawlings-Blake's ability to balance the budget and manage the city would mean more to voters.
Gov. Martin O'Malley will be in the spotlight Saturday evening as his band serenades the mayors after a crab feast at Fort McHenry.
It was O'Malley who snagged the gathering for Baltimore during his tenure as mayor, Cochran said. Cities compete to host the conference, and a panel of mayors picks the location several years in advance, he said.
The conference was born in 1932 when mayors converged on Detroit to discuss how cities could emerge from the Depression, Cochran said. Many of their ideas were incorporated into President Franklin D. Roosevelt's New Deal, he said.
This year, the mayors are expected to pass a resolution asking the White House to hasten the withdrawal of troops from Afghanistan — the first time the group has asked for an end to a military conflict since the Vietnam War, Cochran said.
They will also be questioning Congress' decision to cut Community Development Block Grant funding, the largest direct source of federal assistance to cities, he said.
"It is a challenge for us, because we have irrational decisions being made by this Congress," said Cochran. "They're making cuts on the backs of our cities."
Rawlings-Blake, who co-chairs the conference's council on water, said she wanted to discuss unfunded federal mandates on water and wastewater.
And if Baltimore's police and fire unions get their wish, funding for public safety will also be on the mayors' minds. The unions unveiled a billboard over Interstate 83 on Thursday that welcomes conference attendees — and asks them to "stop cutting police and fire."
The unions had threatened to picket the conference to show their displeasure over Rawlings-Blake's overhaul of their pension plan, but announced this week that they would use the billboard instead.
Conference attendees will see plenty of police while they are in town. Police spokesman Anthony Guglielmi said "several hundred" plainclothes and uniformed officers will be deployed downtown to protect not only the mayors, but a large convention of — convention planners.