Fracking for shale gas has begun for the first time in the UK since it was linked with earthquakes in 2011.
Energy firm Cuadrilla confirmed the controversial process had started at its site in Little Plumpton, Lancashire after a legal challenge failed on Friday.
Protester Ginette Evans said there was a "mood of disappointment" but insisted the fight was "not over".
Cuadrilla insisted the process was safe and would be of "enormous" benefit.
The company's chief executive Francis Egan said: "These are the first exploration wells that will be tested... we have high hopes for them but we have to wait and see what comes out."
If successful, he said it would "lead to tens of thousands of jobs and could be a very significant contributor to the exchequer and... could also reduce emissions because it will be better than importing gas from far afield".
The energy firm confirmed in a statement at 13:15 BST that it would spend at least three months fracking two horizontal wells, and then it would test to see if the gas flow was commercially viable.
If it is, up to 20 wells could be built.
Two protesters closed Preston New Road earlier when they cemented their arms together in a tyre and sat down in the middle of the road. They have since been cut free by police.
Another demonstrator climbed on to scaffolding on top of a van at the entrance to Cuadrilla's Little Plumpton site.
They were served with contempt of court notices for breaching the injunction Cuadrilla obtained preventing trespassers from entering land where fracking is taking place.
Our van blockade plus double lock on is now 9 hours strong at the UK's first frack site on Preston New Road, Lancs ✊— Reclaim The Power (@reclaimthepower) October 15, 2018
We are taking action in solidarity with @frackfreelancs to support their vital work in opposing this toxic industry and defending our climate #WeSaidNo 🌍 pic.twitter.com/xiLYaoQAqi
Campaigner Bob Dennett, who failed to stop the work from beginning in the High Court, said: "They have sacrificed Lancashire to the gods of greed."
"We will do whatever we can to halt [Cuadrilla] in their tracks," he added.
Another campaigner, 87-year-old Anne Power, said she was "so angry" because it would be an environmental "disaster" and said she would continue the fight "as long as she has a voice".
Lee Petts, chairman of Lancashire For Shale pro fracking group, said he was "really pleased" that fracking had finally started after a "long journey".
He said the industry had "huge scope" and could be as big a contributor to the Lancashire economy as BAE Systems.
Cat Smith, Labour MP for Lancaster and Fleetwood, tweeted: "Future generations will look back at this and wonder why we didn't heed climate change warnings."
"The Tories have slashed support for small scale renewables, scaled back support for electric vehicles and are being slammed by a leading climate scientist for its pursuit of fracking."
A spokesperson for the Department for Business, Innovation & Skills said: "Shale gas has the potential to be a new domestic energy source, enhancing our energy security and delivering economic benefits, including the creation of well paid, quality jobs.
"We have been clear that any shale developments must be safe and environmentally sound."
By Roger Harrabin Environment Analyst
The resumption of fracking falls on the day the government launches Green GB week to highlight technologies that combat climate change.
So how can the government stimulate fracking, while also pursuing zero greenhouse gas emissions?
Well, let's look at the timescales.
The first fossil fuel to be banished from the UK is coal. Next will be oil. Gas is least damaging so it will be last. Experts anticipate the UK will be using dwindling amounts of gas until the middle of the century.
Climate minister Claire Perry asks: "Why would you want to import gas when you could create your own?"
Environmentalists say this argument is flawed. They believe by the time the UK develops a shale gas industry it'll be time to close it down.
Second they point out that coal, oil and gas firms have already discovered enough fossil fuels underground to overheat the planet three times over - and a shale gas industry would only add to the problem.
But the Treasury sniffs potential tax revenues and its arguments have won the day in government.