The protests on Saturday took place on the eve of the governing Labour Party's annual gathering.
Protesters packed Manchester's central Albert Square on Saturday before setting off on a march around the conference centre where delegates will meet.
The five-day Labour meeting begins on Sunday.
A few hundred metres from a hotel where Blair and other party officials will stay, families of some of the British soldiers killed in Iraq set up a "peace camp" of a half dozen tents, where they intended to camp out in hopes of getting the prime minister's attention.
The Stop the War Coalition, which organised the march, estimated about 30,000 people were participating.
Police initially estimated the crowd at 10,000, then doubled that figure.
Speakers at a rally outside the conference venue accused Blair of following the United States into illegal wars in Iraq and Afghanistan and failing to condemn recent fighting between Israeli forces and Hezbollah guerillas in southern Lebanon.
George Galloway, an outspoken former member of Labour, told the crowd that Blair "is about to fall, not because of [the]economy, or a great social issue, he is about to fall for one reason ... it is the wars, and the obscene Monica Lewinsky relationship he has entered into with George Bush."
Other speakers included journalist Lauren Booth, sister of Blair's wife Cherie, who lambasted Blair over Lebanon.
"I want him to feel ashamed ... that he didn't push for an immediate cease-fire in Lebanon and let it be flattened," she said.
Blair has said the five-day Labour conference will be his last as party leader. He gave in to pressure from his party two weeks ago to promise he would quit within a year.