The biggest rallies were in New York, Los Angeles and Chicago, where organizers said they wanted to build on the momentum after several nights of protests triggered by the real-estate mogul's surprise win in Tuesday's presidential election.
In New York, several thousand protesters marched peacefully up Fifth Avenue past its glitzy store fronts, some already bearing Christmas decorations, before filling the streets at the foot of Trump Tower, the president-elect's skyscraper home.
"We're horrified the country has elected an incredibly unqualified, misogynist, racist on a platform that was just totally hateful," said Mary Florin-McBride, 62, a retired banker from New York who held a sign reading, "No Fascism in America."
There were also demonstrations in Chicago and Los Angeles, where several thousand protesters gathered beneath MacArthur Park's palm trees holding placards including "Dump Trump" and "Minorities Matter," before marching toward downtown.
Some of the demonstrators waved American, Mexican and rainbow flags. Holding a "Keep Love Legal" sign, 25-year-old gay Los Angeles resident Alex Seedman called Trump a fascist and feared he would repeal marriage equality.
Evelyne Werzola, 46, an immigrant from South Africa, said she had seen what a police state could do.
"I've seen people oppressed. And this is like a heartbreak of the American dream for me," Werzola said. "So I'm fighting to keep what America has stood for alive."
Raising fears of violence around the rallies, one protester in Portland suffered non-life threatening injuries when he was shot early on Saturday as he took part in a march across the Morrison Bridge by a young gunman who fled the scene.
Portland police said later that the suspect's car was spotted, a gun was impounded and four people detained. The vehicle's occupants are believed to be criminal gang associates, the police department said in a statement.
PROTESTS LARGELY PEACEFUL
Since Trump's victory, demonstrators in several cities have decried the Republican's campaign promises to restrict immigration and register Muslims, as well as allegations that the former reality-TV star sexually abused women.
The demonstrations so far have been largely peaceful, although in Portland protesters smashed store windows, sprayed graffiti and damaged cars late on Friday as they clashed with police who used tear gas and rubber bullets to disperse crowds.
Dozens of protesters have been arrested and a handful of police injured.
The demonstrations since the election have been impromptu affairs, quickly organized by young Americans with a diverse array of backgrounds and agendas.
Protesters were at their most numerous and intense in the rallies immediately following the election before getting smaller in scale. Saturday's protests, however, were expected to be bigger due to the weekend.
As activists look to the next four years with Trump in the White House and his party controlling both houses of Congress, some are preparing for what they hope will be the nation's most enduring demonstrations since the Occupy Wall Street movement.
Trump initially denounced the protests and said they were "incited" by the media, but reversed course on Friday and praised the demonstrators' "passion for our great country."
"We will all come together and be proud!" Trump said on Twitter.
Many voters were shocked by the result, after opinion polls failed to predict a win for Trump.
Some 60.3 million people voted for Trump, fewer than the 60.8 million who cast ballots for Clinton. But Trump's strong showing in swing states, including Michigan, meant he triumphed in the Electoral College that ultimately picks the president.
The president-elect's biggest support base was the broad middle of the country, from the Heartland through the Rust Belt, with voters in states that had long supported Democrats choosing Trump after he promised to end corruption in Washington D.C., and bring back jobs by renegotiating international trade deals.