The crowds, chanting "Surround government headquarters!" and "Open the road!", made their way to the buildings in Admiralty, next to Hong Kong's central business district and some of the world's most expensive real estate.
"I urge everyone to stay here until the morning to keep surrounding the government headquarters. Let's stop the government from functioning tomorrow," a protester clad in a black T-shirt shouted into a loud hailer.
Scores of protesters with wooden shields and metal barricades charged police as officers warned them to retreat. Police, who have been accused of using excessive force, struck demonstrators with batons in a bid to push them back.
Hong Kong's pro-democracy protesters are demanding free elections for the city's next leader in 2017, not the vote between pre-screened candidates that Beijing has said it will allow.
The democracy movement represents one of the biggest threats for China's Communist Party leadership since its bloody 1989 crackdown on pro-democracy student protests in and around Tiananmen Square in Beijing.
Demonstrators threw bottles, helmets and umbrellas at police as tensions escalated.
Police used pepper spray in an attempt to disperse the protesters, dragging several to the ground before cuffing them with plastic ties and taking them away. Scores of demonstrators held up umbrellas, which have become a symbol of the pro-democracy movement, to protect themselves from the spray.
The activists tried to reclaim Lung Wo Road, a key thoroughfare in Admiralty district that police cleared more than a month ago during some of the most violent scenes since the demonstrations began in late September.
Two student groups who have led the two-month long civil disobedience campaign had urged supporters to escalate their actions at the main protest site in the Admiralty neighbourhood.
The flare-up comes after four nights of clashes in the working-class district of Mong Kok, across the harbour from Admiralty. Police on Wednesday had cleared the area - one of the city's largest and most volatile protest sites.
The latest clashes underscore the challenges authorities face as a restive younger generation contests Beijing's grip on the financial hub and demands greater democracy.
Twenty-eight people were arrested in the unrest on Friday night and early Saturday in Mong Kok, which is packed with shops, street stalls, jewellery shops and restaurants.
The Hong Kong rallies drew more than 100,000 on to the streets at their peak. Numbers have since dwindled and public support for the movement has waned.
