Protesters from the environmental group blocked Limehouse Causeway at the junction with the A1206 at around 8:20 a.m. Monday.
Metropolitan Police said 52 protesters had been arrested and were in the process of being taken into custody.
In a statement, the campaign group said 61 protesters blocked three locations on Upper Thames Street, Bishopsgate and Limehouse Causeway. Images posted on social media showed drivers pulling protesters from the road and laying them on the sidewalk.
Another clip showed police struggling to eliminate protesters who had stuck to the road.
Police in the City of London confirmed that police officers remained at the scene.
They wrote: “Bishopsgate is currently closed at the junction with Wormwood Street due to protest activity. Police are on the scene, but avoid the area if possible as this will disrupt traffic.
“Police are also at Southwark Bridge, at the junction with Upper Thames Street, which is also closed in both directions, due to protest activity.
“Please avoid the area if possible. “
Protester Tony Hill, who claimed to be a former police officer, soldier and adviser, and said he came from close to Kendal in Cumbria to join the protest in Bishopsgate, said the call from Isolate Britain to isolate all British houses was “obvious.”
The 71-year-old said: “I am here today out of anger, fear and determination.
“We say isolate as many buildings as possible. It is obvious. It’s something we can all do, it’s a solution.
“We have the money; all we need is the will of our government to do it. It will save money, create jobs, save lives and save the planet.
Members of the public heckled protesters blocking the road at the junction of Bishopsgate and Camomile Street.
One man, who shouted as he passed, said: “We all have a job to do. “
It marks a comeback for the protest group after suspending its activities for 11 days following resistance from motorists.
In an open letter to the Prime Minister on October 14, they announced that they would suspend their campaign in the run-up to the COP26 conference in Glasgow.
Isolate Britain – an offshoot of Extinction Rebellion – wants the government to isolate all British homes by 2030 to reduce carbon emissions.
The group blocked roads for 14 days in the five weeks leading up to October 14, with activists often sticking their hands to the pavement to increase the time it takes for police to remove them.
Liam Norton of Insulate Britain said: “We know the public is frustrated and annoyed by the disruption we have caused. They should know that somehow this country will have to stop emitting carbon.
“We can do it now in an orderly and planned manner, insulating homes and preventing thousands of fuel poverty deaths or we can wait until millions have lost their homes and are fighting for water or starve. “