HMS Iron Duke seized more than five and a half tonnes of the drug in an operation off the coast of South America.
In the UK it would have a street value of £240 million, the Navy said.
Minister for the Armed Forces Mr Bill Rammell said: ''Again, the Royal Navy has successfully damaged the trade in this vile substance, which only serves to poison our communities. The crew rightly deserve our praise and thanks for the work they do on our behalf.''
The 138-foot fishing boat MV Cristal was spotted by a Navy helicopter crew in an area known for trafficking, which led to a dramatic swoop with the US coast guard and another British ship RFA Fort George.
In total 212 bales of cocaine were found, weighing about 26kg each. The crews then sank the drug smugglers' boat.
Prince William served on HMS Iron Duke last year when it seized cocaine worth £45 million in the Caribbean.
In July this year, the ship was involved in a night time operation off South America which netted more of the drug, with a street value of £33 million.
Commander Andrew Stacey said that an armed helicopter and rigid inflatable boats were sent to intercept the ship on September 15.
His crew then spent more than 24 hours painstakingly scouring the vessel for narcotics.
The drugs were hidden under the ship's regular stores, beneath a concrete floor and steel panels.
Tonnes of stock had to be moved, the hard floor broken up with sledge hammers and metal panels unbolted before the stash was revealed.
Cdr Stacey said: "This was our third successful drug bust in as many months but this surpasses anything we've had and anything the Navy had previously. It is the largest drugs bust by value, and by volume in terms of cocaine.
"It is a massive blow for the narcotics industry. My team are delighted and all our hard training and preparations have paid off."
After the bust the captured boat was in trouble and getting near a major shipping lane so the naval crew sank it with gun fire.
Several drug runners of different nationalities were arrested but Cdr Stacey could not reveal any more details.
The cocaine was stored on the Iron Duke for around 24 hours - because there was so much of it some had to be kept on deck under armed guard.
Cdr Stacey said: "We are very well prepared to defend ourselves. It was a big quantity and I was conscious of the fact that some people might want it back, but they would have a tough time getting it back from us."
HMS Iron Duke is on a six-month deployment to visit UK overseas territories during hurricane season.
It remains on stand-by to take part in anti-narcotics operations.