The chopper smashed through the roof of the crowded pub, where more than 100 revellers were listening to a band, local time.
Witnesses said the helicopter, carrying two police officers and a civilian pilot, dropped like a stone.
People inside the pub heard a whoosh before the roof caved in.
Firefighters said they had made "some contact" with people in the wreckage of the single-storey building, which was "very unstable".
"It's a case of working hard within the building to try to determine how many casualties are there," said fire brigade officer Lewis Ramsay. "We are determined that we are going to get the building stable and we will carry out those rescues."
Ramsay said the 125 firefighters at the scene had "rescued numerous casualties" who had "multiple types of injuries".
Scotland's First Minister Alex Salmond confirmed that a police helicopter was involved in the "tragic accident".
"Given an incident of this scale we must all prepare ourselves for the likelihood of fatalities," he said.
An AFP photographer at the scene said the helicopter appeared to have smashed through the top of the pub on the banks of the River Clyde.
A rotor blade could be seen protruding from the roof.
Police Scotland Deputy Chief Constable Rose Fitzpatrick said it was not yet known why the Eurocopter EC135 helicopter crashed.
"I can confirm there are a number of casualties but it is too early at this stage to provide further details."
Witnesses told of confusion, terror and bravery after the accident.
Grace MacLean, who was inside at the time of the crash, told BBC News that the revellers were listening to a ska band.
"We were all just having a nice time and then there was like a 'whoosh' noise - there was no bang, there was no explosion," she said.
"And then there was some smoke, what seemed like smoke. The band were laughing and we were all joking that the band had made the roof come down.
"They carried on playing, then it started to come down more and someone started screaming and then the whole pub just filled with dust. You couldn't see anything, you couldn't breathe."
Members of the band, Esperanza, later said on their Facebook page that they were all well.
Labour MP Jim Murphy told the BBC he was driving through the area soon after the incident.
"I jumped out and tried to help," he said. "There were people with injuries. Bad gashes to the head. Some were unconscious. I don't know how many."
He said he and other people formed a human chain to get survivors out.
"The helicopter was inside the pub. It's a mess. I could only get a yard or two inside. I helped carry people out."
The pub is near Glasgow Central Mosque, the largest Muslim place of worship in Scotland. Mosque officials said they would make its premises and volunteers available to help the rescue effort.
The editor of the Scottish edition of the Sun newspaper, Gordon Smart, said he saw the helicopter coming down.
"It was just such a surreal moment. It looked like it was dropping from a great height at a great speed," he told Sky News.
"There was no fireball and I did not hear an explosion. It fell like a stone. The engine seemed to be spluttering."
British Prime Minister David Cameron said: "My thoughts are with everyone affected by the helicopter crash in Glasgow - and the emergency services working tonight."