Around 50,000 people marched through the city during the opening day of the Conservative Party conference, which is being held in Manchester between September 29 and October 2.
Trade unions organised the protest, and put on buses to transport supporters from Glasgow, Edinburgh and Dundee.
The aim of the protest was to highlight the impact of Government policies on jobs and spending across the health service, as well as the "rapid sell-off" of the most lucrative parts of the NHS to private healthcare companies, organisers said.
Greater Manchester Police (GMP) said the protest - said to be the largest ever dealt with by the force - had passed off peacefully in the most part, with just two arrests for breaches of the peace.
TUC general secretary Frances O'Grady said the march and rally allowed thousands of ordinary people to show the Government exactly what they thought of its policies.
He said: "Austerity is having a devastating effect on our communities and services, with 21,000 NHS jobs lost over the last three months alone."
Following the march a rally was held where union leaders, politicians, celebrities and NHS workers addressed the crowd.
Len McCluskey, the General Secretary of Unite, told the rally that David Cameron and Nick Clegg's talk" of "re-organisation and reform" really meant "fragmentation and privation."
He added: "They don't value the health of ordinary people. They only know how to put a price on it.
"Our message to Cameron is crystal clear: you will have to come through us, though the ballot box, to take our National Health Service from us," he said.
Coronation Street actress Julie Hesmondhalgh, who plays Hayley Cropper in the soap, paid tribute to the NHS which she said had saved her husband's life.
The actress said she owed the NHS "everything" and wanted to be part of stopping the NHS from being "dismantled".
Shadow health secretary, Andy Burnham, addressed the rally calling it an "unbelievable show of action for the best health service in the world."
He said it was an "incredible message of solidarity" to health service staff who were "under attack" from the Government.
"What a message you have sent today to an arrogant, out-of-touch, Prime Minister," said Mr Burnham to cheers.
"David Cameron, are you listening? You have never been given permission to put the National Health Service up for sale. That's the message coming out of this rally today," the MP for Leigh said.
Mr Burnham pledged to the rally that the next Labour Government would repeal the Health and Social Care Act 2012 and would "put people before profit".
But as he spoke some protestors shouted: "You must keep your word" and "hypocrite" and accused Labour of privatising the NHS when it was last in power.
Leading musicians also helped to organise the event in signs of a renewed link between music and politics.
Manchester musician John Robb compered the rally, while Liverpool band the Farm, and 15-year-old John Lennon McCullagh performed.