Flanked by police in riot gear, the protesters moved through the fortified city, loudly and exuberantly chanting slogans such as "No more years." They accused the Bush White House of prosecuting an unjust war in Iraq, making the country poorer and undermining abortion rights.
There were no reports of major violence and about 100 scattered arrests.
Police gave no official crowd estimate, though one law enforcement official, speaking on condition of anonymity, put the crowd at 120,000; organizers claimed it was roughly 400,000. The line of protesters stretched more than two miles long, CBS News Correspondent Jim Axelrod reported.
The march snaked in a circular route around midtown Manhattan, shutting down dozens of blocks and bringing out hordes of police in a city already girded against terrorist attacks.
"They chose New York, where they're universally hated," said writer Laurie Russo, 41, of the New York borough of Queens. "They should have gone somewhere they're more welcome. They exploited 9-11 by having it in New York at this time."
In the largest set of arrests, some 50 protesters on bicycles who stopped near the parade route were carted away in an off-duty city bus. Also, 10 people were arrested after someone set a paper dragon float afire near Madison Square Garden, site of the convention, and nine demonstrators tried to prevent the arrest, authorities said. The nine were charged with assault.
"There's been a few minor arrests," Mayor Michael Bloomberg said. "It has been peaceful."
Residents leaned from windows along the demonstration route to shout their support. Scattered opposition was visible only around Madison Square Garden, where the GOP convention opens Monday. Some early convention arrivals looked across police lines, shouting at demonstrators: "Go home!"
"I hope this shows the world that they're not alone in their hatred of George Bush," said Alan Zelenki of Eugene, Ore., who planned for three months to attend this week's protests.
The causes varied as much as the people shouting support: immigrants' rights, gay rights, universal health care, the Palestinian cause, an end to the killing in Sudan. Tracy Blevins, a biomedical researcher who recently left New York for Houston, dyed her Maltese pink and carried the little dog in a baby pouch to advocate peace.
Some demonstrators batted around a 6-foot-wide inflatable globe. One sign echoed Democratic nominee John Kerry's Vietnam-era remark: "How do you ask a soldier to be the last person to die for a lie?"
Karen Nicholson, 67, of Charlotte N.C., said she and her 34-year-old son flew up to New York just for Sunday's rally.
"You've got to do something," she told CBSNews.com's Jarrett Murphy. "You do what you can. It just makes a statement of the groundswell that is against this administration and its policies."
Laura Trainor of New Jersey was with a group of about 40 people carrying flag-draped coffins meant to represent U.S. soldiers killed in Iraq.
"I think sometimes you need a visual representation of what's going on over there," said Trainor. "A lot of people dying over there might not have the voice to speak out against something. This gives those people a voice."
Among the marchers were people who had lost loved ones in the Iraq war. Celeste Zappala's son, Sgt. Sherwood Baker, died serving the Pennsylvania National Guard in Iraq just four months ago.
"I swore at my son's funeral I would not be quiet," Zappala told CBS News Correspondent Jim Acosta. "He doesn't get to come back and say, 'Oh I'm sorry we made a mistake. There are no weapons of mass destruction.' He never gets that chance."
"And now, today, here the people say 'no more Bush in the white house. End the occupation in Iraq,'" said Fernando Suarez del Solar, whose Marine son Jesus was killed just days after the fighting stated. "I paid the last price. I paid with my son's life."
The protest organizers, United for Peace and Justice, had sued unsuccessfully to force the city to allow a rally in Central Park. City officials said such a rally would damage lawns.
A crowd of a few hundred demonstrators did gather in the park after the march. They chanted and formed a large peace sign, but police officers stayed at the margins of the unofficial demonstration and did not appear poised to make arrests.
"Fahrenheit 9-11" director Michael Moore told demonstrators that "the majority of this country opposes the war ... The majority are here to say, 'It's time to have our country back in our hands.'"
On Friday, 264 people were arrested for disorderly conduct in a bicycle ride that snaked through the city and passed by Madison Square Garden.
A number of other events were planned Sunday, including a gay rights demonstration and a vigil in Central Park by a group of Sept. 11 families opposed to the Iraq war.