"Earlier this morning, a WFP plane dropped the first cargo of 21 tonnes of items into Deir Ezzor," Stephen O'Brien told the UN Security Council.
Reports from aid teams on the ground confirm that "pallets have landed in the target area as planned", he added.
UN agencies are working to scale up aid deliveries to Syria before a cessation of hostilities enters into force at midnight Friday to shore up peace efforts.
Russia airdropped aid to the eastern town of Deir Ezzor in January as part of its campaign in support of Syrian President Bashar al-Assad.
Also Read
The UN aid chief said some 110,000 people living in besieged areas had received aid and that deliveries to a further 230,000 people including through air drops had been approved.
"We are still waiting for approval for an additional 170,000 people. We expect those approvals to happen immediately," he said.
The United Nations is calling on all sides to lift starvation sieges across Syria, where it estimates that 487,000 people live, although some non-governmental organizations say the figure is much higher.
More than 260,000 people have died in Syria's conflict, which began in March 2011 with anti-government protests but has since imploded into a multi-sided proxy war.