Crowds marched towards parliament in Athens, beating drums and blowing whistles as part of the 24-hour strike.
Minor clashes broke out at one stage when police fired tear gas at hooded youths throwing stones.
The strike has been called by Greece's two biggest trade unions, representing half the four million-strong workforce.
"We are protesting about pensions, emergency taxes, the high cost of life," retired factory worker Kyriakos Anastassiadis told the Associated Press.
The strike shut schools and left hospitals with emergency staffing. Domestic flights and long-distance train services were cancelled.
Ilias Iliopoulos, secretary-general of Adedy public sector union, said the strike was an attempt to "get rid of the bailout deal".
"A social explosion is very near," he said.
Demonstrations were also being held in Crete and in the second-largest city of Thessaloniki, where some 17,000 people protested peacefully.
The strikes come days before international lenders are due in the capital to discuss the next instalment of a bailout.
The debt-ridden country is being kept afloat by billions of euros from other eurozone countries and the International Monetary Fund.
In return, the government has imposed waves of unpopular spending cuts and tax rises, hitting pay and pensions and sending unemployment soaring to more than 26%.
Strikes and violent protests have become commonplace.
Greece's coalition government secured the latest tranche of bailout money at the end of last year, and Finance Minister Yannis Stournaras told the BBC the worst was over for his country.
However, the BBC's Mark Lowen in Athens says the strike is a reminder that government confidence in a slowly improving economic situation is not shared by many on the streets.
Our correspondent says the only difference between Wednesday's strike and earlier protests is that public transport has been largely unaffected.
Prime Minister Antonis Samaras's eight-month-old government has taken a tough line on strikers, invoking an emergency law twice in recent months to order seamen and metro staff back to work.
But despite such measures, strikes have recently picked up.
A one-day visit by French President Francois Hollande on Tuesday went largely unreported because Greek journalists were on strike.
Our correspondent says more than 20 general strikes since the crisis erupted have failed to change government policies, and this one is unlikely to be any different.

Sum: Tens of thousands of Greeks are taking part in the first general strike of 2013, as workers renew their protest over austerity measures.


Julie Fallon's brother Andrew Sefton, 23, was one of 96 fans who died.
She said families were sitting through traumatic evidence and that having to listen in silence made it doubly tough.
Charlotte Hennessy, whose father James died in the disaster, told the BBC the inquests in Warrington had "opened up a whole new grieving process" for her.
The new inquests were initially expected to last nine months, but may now continue until early 2016.
Events of 15 April 1989, which resulted in the deaths of 96 football fans, have never been scrutinised in so much detail.
Over the past year the jury has examined the safety of the stadium, which one expert said had its terraces' capacity set too high.
For the first time, the way the emergency services responded has been analysed fully in court.
And the jury has heard claims of a police cover-up - allegedly designed to deflect blame on to the fans.
But the evidence began on March 31 last year with emotional portraits of those who died.
In Mrs Fallon's statement read to the jury, she said: "My brother's life was like a book that had a title, an introduction, described the characters, set the scene and then someone ripped out the rest of the pages."
Mrs Fallon has been a regular at the hearings but now plans to dramatically cut the number of days she attends - restricting herself to those directly relevant to her brother.
She said: "You can see the strain up close.
"You can see the fact that people's heads are bowed, the fact that they're tense, the fact that, you know, some people are crying.
"It's palpable because you're in amongst it and that is really difficult to sit amongst, day after day."
For the past year Charlotte Hennessy has been juggling bringing up her three boys with going to the inquests.
Her father James Hennessy, known as Jimmy, was 29 when he died - she was aged six.
She said: "I don't think I was prepared for quite how traumatic it would be.
"I think that maybe it's opened up new wounds, but it's opened up a whole new grieving process for me because I was so little."
Ms Hennessy said she attended 10 days in a row around the time of former match commander Ch Supt David Duckenfield's evidence.
"To be honest I don't remember most of it, [because] you're just getting up, driving there, driving back, making tea, going to bed," she said.
"I felt really sorry for the boys then because they [have] hardly seen me."
"I'm hoping that once this is all over, I can have a life without Hillsborough and it doesn't take any more of my children's lives."
The evidence at court is now moving into how South Yorkshire Police gathered statements after the disaster.
There will then be individualised hearings for all of the 96 who died.
For Ms Hennessy and the rest of the families, it is a process that is set to last for at least several months.

Sum: A woman who lost her brother in the Hillsborough disaster says she can no longer face regularly attending the inquests, one year after they began.


The European Parliament is debating a motion expressing concern at the political impasse in Northern Ireland.
Talks involving the British and Irish governments and the five executive parties are continuing at Stormont.
Mr Robinson said he had been stressing in Brussels that they "genuinely and sincerely want to get a satisfactory outcome to the talks process".
"We are going to put everything we have into getting that outcome," the DUP leader said.
"Until you come out with agreements at the end of a process, there's always scepticism and I think that's something you have to take for granted.
"It gives us the encouragement to try and prove the sceptics wrong."
Speaking in Brussels ahead of Wednesday's debate, he said: "In the early parts of any talks process, people keep their cards close to their chest - they state their positions, and it's really at the latter end of it that you test the other people who are around the table to see how far they are prepared to go on various issues."
The motion being debated by MEPs has been endorsed by a cross-section of parliamentary groups, and has been signed by Sinn FÃ©in's Martina Anderson and the UUP's Jim Nicholson.
It expresses concern that the implementation of the peace process has reached an impasse, and urges all parties "to work constructively towards a lasting resolution of the conflict and the full implementation of the Good Friday Agreement and subsequent agreements for a long-lasting and enduring peace".
It says continuing violence by "fringe elements" is undermining the peace process, and "stresses the need to combat such criminal activity by tackling existing economic challenges such as unemployment and low incomes and living standards".
The motion also says the European Parliament stands ready to offer any assistance it can to political parties in Northern Ireland.
It invites Northern Ireland's first and deputy first ministers to address the European Parliament "upon the successful completion of the all-party talks".
Both Mr Robinson and Ulster Unionist leader Mike Nesbitt have been in Brussels this week ahead of Wednesday's debate.
Deputy First Minister Martin McGuinness of Sinn FÃ©in briefed European parliamentarians last month.

Sum:
First Minister Peter Robinson has said he appreciates the "support and encouragement Europe has given us".