The mosquito-borne disease kills hundreds of thousands of people a year, the vast majority of them in Africa.
The WHO said malaria was responsible for 435,000 deaths around the world in 2017.
The drone, provided by the Chinese company DJI, sprayed mosquito-infested rice fields in Zanzibar with a silicone-based liquid to create a thin film over the stagnant water.
The idea is that this will cause mosquito pupae and larvae to drown and die, according to a statement issued by DJI on Thursday.
The company said liquid is “non-toxic and biodegradable,”
The researchers hope that the method will “significantly” reduce the mosquito population, which was being assessed before, during and after the spraying in late October.
Scientist Bart Knols, who is carrying out the anti-malaria drone project together with entrepreneur Guido Welter and University of Nairobi professor Richard Mukabana, said that using drones is “essential.”
“Spraying by hand is very time-consuming and using a helicopter is too expensive and simply not realistic,” he said.
Mukabana said that the project was “the first attempt to fight malaria with spray drones on such a large scale.”