Just hours before US President George W Bush arrived, crowds threw stones and chanted slogans against the US leader.
Up to 250 people were arrested on the fourth day of confrontations between police and protesters.
Mr Bush and Russian leader Vladimir Putin are to attend the summit, where talks will focus on security and trade.
'Go away'
Thousands of police have been deployed throughout Santiago to break up unofficial protests ahead of the summit.
The authorities declared a holiday on Friday but up to 25,000 people marched through Santiago in protest against capitalism and US policies.
"This gathering is not authorised. Go away," a loudspeaker mounted on a police water cannon told protesters.
Protesters responded by throwing stones at the vehicle and shouting slogans, including "No to Apec, No to Bush, No to capitalism", the AFP news agency reported.
"We have to do something to humanise this economic model that is now spreading in the world," one of the protesters said at an authorised rally that passed off peacefully later.
Widened agenda
Apec's 21 members account for more than half of the global economic output and almost 50% of all international trade.
The bloc was set up in 1989 mainly to promote trade among the Pacific rim countries.
Apec summits have a habit of being overshadowed by other issues, and this year's looks set to be no different, says the BBC's Elliott Gotkine in Santiago.
But inside the convention hall, the leaders are due to discuss ways to combat terrorism.
There are also hopes that Apec could take steps towards creating a free trade area for the Asia-Pacific region, our correspondent adds.
Mr Bush will meet Chinese President Hu Jintao and Russian leader Vladimir Putin in one-on-one meetings.
The US leader is expected to press for new talks with North Korea over its nuclear plans.
On Friday, China said the biggest barrier remained "the extreme mutual distrust between Washington and Pyongyang.
But "you can never push too hard for a good purpose," said Kong Quan, spokesman for the Chinese foreign ministry.