The biggest show of people power was in Baltimore itself, where several thousand mostly young demonstrators paralyzed several city blocks in a major rally through downtown to City Hall.
Thousands more protested in New York, Boston and the capital Washington in solidarity.
The protests were overwhelmingly peaceful and good-natured, although New York police detained several demonstrators and emotions were running high.
What appears to be a growing movement for change was centered on Baltimore, where a rally that started at the main train station included black and white demonstrators, some of them linking arms and chanting: “No justice, no peace! No racists, no peace!”
Many in the march, which appeared to be gathering momentum, were high school or college students.
“We’re protesting the ongoing injustices that police have perpetrated on black men particularly. Police are trigger-happy and we need to stop that,” Jonathan Brown, 19, a student at Johns Hopkins University, told AFP.
And he warned: “If you can’t get your way through non-violent means because the aggressor is violent, other action needs to be taken.”
Some in the huge crowd held placards, one reading, “Killer cops deserve cell blocks.” A few wore shirts with the words, “Amnesty International observer.”
The 2,000 National Guard personnel who have flooded Baltimore this week kept a low profile, although authorities have said they are primed to swoop should the march spark unrest like that which flared following the funeral of Freddie Gray, 25, on Monday.
Gray’s death was the latest instance in the United States of a black man succumbing at the hands of police — a situation that has stirred resentment among African Americans who believe they are targeted by police.
That anger also sparked coast-to-coast demonstrations in major US cities last year after a white policeman shot dead an unarmed black teenager in the St Louis suburb of Ferguson in August.
Baltimore authorities urged calm and warned that they would again enforce a citywide curfew beginning at 10:00 pm (0200 GMT Thursday) and lasting until 5:00 am.
Tuesday night’s curfew was largely respected, although police made 35 arrests during the night and warned that they were assessing the volatile situation minute-by-minute.
Maryland State Governor Larry Hogan said he had been “very encouraged” by the last 24 hours and said a semblance of normality was returning to Baltimore, a gritty city of 620,000 about an hour’s drive from Washington.
But he cautioned: “We are not out of the woods yet.”
And he warned demonstrators to respect the curfew: “There are peaceful protests happening tonight. We want to make sure individuals can exercise their First Amendment rights and express their concerns.
“We also want to stress and remind everyone that there is a 10:00 pm curfew in place in the city and I urge everyone in Baltimore to get off the streets at 10:00 pm.”
– New York arrests –
In New York, protesters gathered at Union Square, in Lower Manhattan, for a rally dubbed on a Facebook page, “NYC Rise up and Shut it down with Baltimore.”
“We call on New Yorkers from across the five boroughs, #BlackLivesMatter activists and organizations as well as all organizations that stand for social, economic, and racial justice to rally,” said the organizers.
The march initially met no resistance from police, but that swiftly changed as officers moved in and made arrests.
New York Police Department would not say how many were detained, though CNN put the number at a couple of dozen.
Smaller demonstrations were held in Boston and Washington, US media said.
– Empty stadium –
Baltimore police made 18 arrests during the day on Wednesday, said police Commissioner Anthony Batts, but there was no immediate repeat of the violence and looting that broke out after Gray’s funeral.
Police said they were keeping a keen eye on social media — used by protesters to coordinate their action.
Amid the violence on Monday, the Baltimore Orioles postponed two Major League Baseball games against the Chicago White Sox.
For Wednesday’s contest at Camden Yards, they closed the stadium to fans.
The 8-2 victory for the home team was played before empty stands.
Among the many startling images to emerge from the riots in the city was that of an infuriated mother hitting her teenage son repeatedly for joining the demonstrations on Monday and dragging him away.
“I just lost it,” said Toya Graham, a single mother of six.
“I was shocked, I was angry, because you never want to see your child out there doing that,” she added, speaking to CBS News.