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Part of the A40 has been partly closed as groups of between 20 and 30 vehicles will park on it while others are travelling in police-led convoys into the city centre.
A group of drivers has also gathered in Westminster. A demonstration last month caused widespread disruption.
Hauliers are demanding a 25p-in-the-pound tax rebate on diesel.
The average price of diesel is now £1.32 per litre and lorry drivers say this leaves them with huge fuel bills of up to £1,000 a week for an average articulated lorry.
Hauliers congregated at Medway Services in Kent on Wednesday morning before setting off along the M2 towards London at around 8am.
A second convoy set off from Gateway Services on the M1.
The Road Haulage Association (RHA) which has not endorsed previous demonstrations is joining in the action.
Andy Boyle, National Chairman, said: "The harsh reality is that the price of fuel is now forcing many hauliers out of business. For many, Wednesday will represent a last ditch attempt at making their voice heard.
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"It is therefore absolutely vital that Government not only listens to us but takes urgent action. For those present on Wednesday, whether they be hauliers or members of Parliament, doing nothing is no longer an option".
Peter Carroll, spokesman for Transaction said: "Our industry is being driven out of business. Continental hauliers are able to run in the UK using cheaper fuel from abroad. The Government needs to realize that the surge in Oil prices has changed the world.
"It is madness to insist on charging the highest level of fuel duty in the EU on top of a world price that has rocketed. If nothing is done, thousands of UK hauliers will go bust. We have sound and effective proposals to solve this problem. The Government needs to talk to us and to listen to us".
RHA Chief Executive, Roger King said: "With world oil prices continuing to rise, the RHA believes that fuel taxes for professional users need a thorough overhaul."
One of the drivers participating in the protest, Paul Prout said its "very sad" and that if he can't make any money running lorries he will have to "pack up and go work for someone else".
Stuart Hosie MP, from the Scottish Nationalist Party has told protestors that ministers "could and should" help those struggling because of rising fuel prices.
He said the government "which takes in massive amounts of money" has an "obligation to put some back".
Chancellor Alistair Darling is now under pressure to scrap the 2p increase in fuel duty planned for October.
Business Secretary John Hutton is believed to be urging Mr Darling to make a statement on the issue before the summer Parliamentary recess.
See: Fuel Price Protest Hits Motorists
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