The World Health Organization (WHO) says the disease killed 435,000 of the 219 million people who were infected last year.
The drones the researchers fly carry the innovation they say offers a new approach in fighting the deadly disease.
The drones sprayed mosquito-infested rice fields, typical breeding grounds for malarial mosquitoes, with Aquatain AMF, a non-toxic colourless, solution.
The liquid, which has been tested in laboratories but never before in the field, creates a thin film on the water's surface preventing malarial pupae and larvae from breathing at the surface, drowning and then killing them.
Researchers said that using drones in this manner will prove efficient and cost effective, especially in large irrigation areas.
"As you can see the way the paddies look like, it is very difficult to just walk through the paddies and apply the chemicals so you want to have something that can just spray it on the water surface, it spreads, does the job and that's it," said Professor Wolfgang Richard Mukabana from the University of Nairobi, one of the researchers behind the project.
Sub-Saharan Africa accounted for 90 percent of malaria deaths around the world, the WHO said. It is one of the major causes of death among children under the age of five, according to the United Nations. Globally, malaria kills a young child every single minute and causes 75 percent of all under five deaths.
In Tanzania, 70,000 people die annually from the mosquito-transmitted disease. The researchers said that they will sample the larvae and the mosquitoes in the fields before, during and after spraying to test the impact of the approach.
"This is where the problem starts. These are the breeding grounds of mosquitos. Once we control them here we will see far fewer mosquitos making it to the house-holds where people live, biting these people and therefore transmitting malarial disease. So by controlling them right at the source we hope to have an impact ultimately on the transmission of malaria," said vector biologist, Bart Knols.
After the trial in Zanzibar, the researchers aim to publish their findings in peer-reviewed journals, they said, and hope to expand the approach across the continent.
"In future if this goes well and we get good results from the trial, we may be using the same technology in many other parts of Africa where they have irrigated agriculture and malaria problems. If not that we may in some case actually be contributing to the elimination of malaria in a specific country," Knols added.
The researchers say they chose Zanzibar for the trials because of its progressive laws towards the use of drones.
Other countries in Africa have deployed drones in the fight against malaria.
Malawi has used drones to map mosquito breeding sites but the researchers in Zanzibar say spraying Aquatain takes the malaria fight to the next level.