More than 4,500 pounds (2,000 kilograms) of the addictive drug were wrapped in paper packages painted to look like the juicy fruit and hidden amongst other cargo.
Border agents pulled over the produce-laden tractor-trailer at Otay Mesa in California on Friday and got in amongst the cargo for a closer look.
There they discovered more than 1,200 watermelons were actually bundles of the synthetic drug wrapped in colored paper, US Customs and Border Protection said this week.
The load was seized and the 29-year-old driver was handed over to Homeland Security.
Meth is a powerful stimulant that can be prescribed by doctors to treat ADHD. But it is also abused as a street drug for its invigorating rush and the feelings of invincibility it can give to users.
The drug, known by various street names, including Ice, Chalk and Scooby Snax, was featured in the hit TV series "Breaking Bad" about a chemistry teacher who descends into a life of crime.
It is often manufactured in crude home laboratories, made by mixing household chemicals and cold medicines. The volatile substances involved are, however, prone to exploding.
