The forced destruction threatens one of France's most classic stretches of scenery. The canopy of trees arching over the canal is a favourite with tourists and locals alike.
The canal runs from the city of Toulouse to the Mediterranean port of Sète. It was commissioned in 1666 by Louis XIV and, together with the Canal de Garonne, acts as a shortcut between the Atlantic and the Mediterranean.
The culprit is the Ceratocystis platani fungus, which is believed to have arrived in the wooden ammunition crates of American servicemen in 1945.
Since its discovery in 2006, it has grown rapidly and threatens all 42,000 of the canal's trees.
"That doesn't mean they will all have to be destroyed," said Jacques Noisette, a spokesman for the French waterways (VNF), quoted in newspaper France Soir.
He claimed specialists are "doing everything to keep them alive."
Protecting the famous trees is critical if the canal is to keep its 1996 designation as a Unesco world heritage site, although Noisette hoped this was not under threat. "Unesco can't threaten to delist the canal when we are the victims of this fungus," he said. "However, they would be entitled to do that if we didn't have solutions in place to replace them."
Two replanting programmes have already been devised, each using different trees. The first will use a special hybrid of the tree that is resistant to the fungus. The second will plant ash trees. "The idea is to avoid using just one type of tree, otherwise next time there's another disease the whole lot will come crashing down again like a house of cards," said Noisette.
President Sarkozy pledged his support in a visit to the region on Tuesday. He told local officials the government would stand alongside them to "save" the canal.
Locals were taking the sad news in their stride. Newspaper France Soir reported the local tourist office as saying the loss of trees wouldn't stop people using the canal. "If there's been a drop in tourism it's more the fault of the weather than the plane trees," said a spokesperson.