The marchers passed the Madison Square Garden convention site on Eighth Avenue as Republicans and visitors converged on New York for the gathering that is expected to culminate with the party renominating Bush for president.
The start of the march on Sunday took on a carnival-like atmosphere with people carrying large and colourful banners, shouting "No More Bush" and beating drums in temperatures hitting 29C.
Many held banners and signs such as "Say No to the War Economy", "Bush Must Go" and "Bush lied, thousands died" in opposition to the war.
The Bush administration said it invaded Iraq to remove Saddam Hussein from power because he had weapons of mass destruction that threatened America's security and he refused to disarm. But no such stockpiles have been found.
New York City police said more than 300 people had been arrested as of Saturday night for disorderly conduct and convention-related incidents.
The circular route was to take the marchers through central Manhattan and activists vowed to defy a ban on rallying in Central Park, the city's largest open space, later in the day.
Protesters were denied a permit to gather in Central Park after the march because they might damage the grass, city officials said. But organisers of some groups urged people to make their way to the park for a "people's picnic" after dispersing peacefully at the end of the march.
Protesters have displayed many
banners denouncing the war
Organisers and a series of prominent speakers including civil rights activist Jesse Jackson, film maker Michael Moore and some New York elected officials boosted the protesters with speeches before the start of the event.
Call to withdraw
"Today, we send our message," long-time activist Leslie Cagan said. "We come from all walks of life ... from cities and towns across this nation and together we will march and in a resounding, clear voice we will say 'no' to the Bush agenda."
Cagan and other speakers called for the US to immediately withdraw its troops from Iraq.
Kelly Doherty, a military police sergeant who served in Iraq for a year and helped establish Iraq Veterans Against the War, said Iraqis and Americans had been "dehumanised" by the conflict.
"This is also dehumanising United States' troops who are also having their sense of patriotism and loyalty perverted and used by an administration that would send our women and men to fight, die and kill for lies," Doherty said.
Security around the arena has been called the tightest in the history of US political events with thousands of police officers and Secret Service agents on guard.
Many Americans believe their
country needs a new president
Streets were closed and concrete barriers put in place to deter car or truck bombs amid warnings from the government that al-Qaida or other groups might attack the US during the election season.
Sunday's march took place as 50,000 visitors arrived in New York City for the four-day convention to nominate the president for a second term in the White House. He is to face Democratic candidate Senator John Kerry of Massachusetts in the November election.
Meanwhile, one of the US' biggest Olympic hero accused Bush of exploiting the Athens Games for his own political advantage. Nine-time Olympic gold medallist Carl Lewis condemned Bush for using the presence of Iraqi and Afghan teams in Athens to boost his election campaign.
"'I felt that was disingenuous. It is funny that we boycotted the 1980 Games [in Moscow] in support of Afghanistan, and now we're bombing Afghanistan," he told the Athens News on Saturday.
"Of course, we've invaded Iraq and are in there and are using it for political gain. It bewilders me and I understand why the Iraqi players are offended."
Lewis was referring to comments made by Iraq's Olympic football team who criticised Bush for using their remarkable achievement of placing fourth in the tournament, to highlight his presidency.
"My problems are not with the American people," Iraq's coach, Adnan Hamad told a monthly sports magazine.
"They are with what America has done in Iraq: Destroy everything. The American army has killed so many people in Iraq. What is freedom when I go to the [national] stadium and there are shootings on the road?"