As they have since the start of the week, protesters on Wednesday choked roads and blocked traffic with anything they could lay their hands on including bricks, bicycles, couches and other materials. Key routes were targeted in morning and after-work peak hours.
Various lines on the subway - used daily by more than half of the city's 7.5 million people - were also suspended, forcing many workers to stay at home.
In the Central business district, hundreds of people left their offices at lunchtime to join the more hardcore protesters setting up barricades outside luxury-item shops and headquarters of big financial firms.
Masked protesters dressed in their signature black were also locked in a series of tense standoffs at university campuses, following intense clashes on Tuesday night that saw police fire tear gas and rubber bullets.
Authorities said 58 injured people - one of them in critical condition - were taken to hospitals during Wednesday’s unrest.
Hospital authorities did not provide details on the critical case, but local media reported that a 70-year-old man was seriously hurt from a suspected hit in the head with a brick during a clash between protesters and residents in the Sheung Shui district.
Highlighting the growing security fears, mainland Chinese students began fleeing Hong Kong on buses and boats back across the border, according to police and universities, although it was not immediately clear how many had left.
The chaos was part of the largely leaderless protest movement's new strategy branded "blossom everywhere", in which small groups target as many parts of the city as possible to cause maximum disruption and stretch police resources.
Until this week protesters had largely confined their actions to evenings and the weekends.
The campaign began on Monday with an effort to shut down trains and enforce a city-wide strike, and has for the first time seen three straight days of chaos during the working week.
"The rioters' intention is to bring Hong Kong into a total breakdown. No excuse, no political motives can justify or glory this madness," police spokesman John Tse told reporters on Wednesday.
A day earlier, one of his colleagues said Hong Kong was "on the brink of total collapse".
The poisonous atmosphere worsened on Monday morning when a police officer shot an unarmed 21-year-old protester, leaving him in a critical condition.
It was only the third confirmed instance police had hit someone with live rounds since the unrest began in June.
The shooting, broadcast live on Facebook, exacerbated fury among protesters about what they say is excessive police violence.
However, fears have also risen about increasingly violent tactics from the protesters.
A masked person on Monday doused a 57-year-old man, who had been arguing with protesters, with a flammable liquid and set him on fire.
He was also hospitalised in critical condition.