The clashes took place after more than 50,000 people marched to parliament on a day of strikes against a new round of cuts demanded by European Union (EU) and International Monetary Fund (IMF) lenders.
As the rally ended, dozens of black-clad youths threw stones, petrol bombs and bottles at riot police, who responded with several rounds of tear gas.
Police chased the protesters through Syntagma Square in front of parliament as helicopters clattered overhead. Smoke rose from a small blaze in a corner.
The strike, called by the country's two biggest unions representing half the four-million-strong work force, is shaping up to be the first test of whether Prime Minister Antonis Samaras can stand his ground.
Police officials estimated the demonstration was the largest since a protest in May last year, and among the biggest since Greece first resorted to aid from international lenders in 2010.
The traditional summer break has let the fragile conservative-led coalition enjoy relative calm on the streets since narrowly coming to power on a pro-euro, pro-bailout platform, but unions predict an end to the lull.
"Yesterday the Spaniards took to the streets, today it's us, tomorrow the Italians and the day after – all the people of Europe," Yiorgos Harisis, of the Adedy public sector group, told demonstrators.
"With this strike we are sending a strong message to the Government and the troika that the measures will not pass even if voted in parliament, because the Government's days are numbered."
About 3000 police, twice the number usually deployed, stood guard in the centre of Athens, which last saw serious violence in February when protesters set shops and banks ablaze as parliament approved an austerity bill.
Police formed a barricade outside parliament, and officers blocked a pensioner who tried to move towards Mr Samaras's office holding a banner with pictures of Greek prime ministers under the title: "The biggest traitors in Greek history".
Ships stayed docked, museums and monuments, including the Acropolis, were shut to visitors and air traffic controllers walked off the job for a three-hour stoppage.
Much of the union anger is directed at spending cuts worth nearly €12 billion (£9.5bn) over the next two years that Greece has promised the EU and IMF in an effort to secure its next tranche of aid.
The bulk of those cuts is expected from cutting wages, pensions and welfare benefits.
l Spain is in a deep recession, its national bank warned, a day after clashes in Madrid between protesters and the police led to 38 people being arrested and 64 injuries.
The demonstrations against the Government's austerity drive at a time of mass unemployment put in sharp relief the scale of discontent brewing in a country suffering its second recession in three years and a jobless rate of nearly 25%.
In the wake of the clashes and a warning from the central bank that the economy continues to shrink "significantly", financial markets have grown nervous.