Officers intercepted a truck carrying 55 million methamphetamine tablets and more than 1.5 tonnes of crystal meth, the UN's crime agency said.
The discovery came after police stopped a truck carrying beer crates in Bokeo, which borders Thailand and Myanmar.
The area - known as the Golden Triangle - has a long history of being a major drug-producing hotspot.
Jeremy Douglas, Southeast Asia regional representative for the United Nations Office on Drugs and Crime (UNODC), told the BBC it was "by far the largest seizure in the history of East and Southeast Asia".
The record bust comes after police recently seized a combined 16 million amphetamine tablets in two separate operations in the same area over a one week period.