Ecstasy tablets with a street value of £750,000 have been seized in an operation which began in Belgium, moving onto London then Wales
More than 40kg of the drug was found by police working from three countries. Five men were arrested.
The drugs haul destined for Wales was secretly intercepted by police at a Belgium depot - six boxes containing 160,000 ecstasy tablets were found.
Police say it was "the biggest ever consignment of ecstasy" seized.
The operation was run by the Metropolitan Police, the Southern Wales Regional Task Force, Gwent Police and the Belgium authorities.
On Friday six boxes containing the drugs were seized by police in Belgium - officers had received a tip off giving information about the planned delivery of the drugs to the UK.
To put this seizure into context, it represents one ecstasy tablet for every 18 to 24 year-old in Wales
Det Ch Insp Colin Richards
On Monday morning, just after 0900 BST, officers watched as a Dutch man went to a depot in north London to collect what he thought were six boxes of drugs.
He loaded them into a car and drove to a meeting with two man in an parked car nearby.
The Dutch man then swapped cars with the two men who then drove their cargo west to the M4.
Specialist drug units followed the car as it headed to south Wales and stopped outside a property in Godfrey Road, Newport.
As the boxes were opened at the property, police raided the house and arrested four men. A fifth man was later arrested.
Police carried out a search of the house and discovered a further 10,000 ecstasy tablets and a quantity of powder, believed to be amphetamine sulphate.
The five men arrested are all from the south east Wales area and are in custody at Newport.
Det Ch Insp Colin Richards, from the Southern Wales Regional Task Force, said: "To put this seizure into context, it represents one ecstasy tablet for every 18 to 24 year-old in Wales and with a street value of around three-quarters of a million.
"The collaborative efforts of law enforcement agencies has prevented the biggest ever consignment of ecstasy reaching the nightclubs of south Wales."