Ukraine's foreign minister hailed a "day of relief for the world" after the Razoni left the Black Sea port, heading for Lebanon via Istanbul with 26,000 tonnes of grain.
The EU, Ukraine and Russia have all welcomed the departure of a ship carrying Ukrainian grain from the port of Odesa, the first since Moscow's invasion in February blocked shipping through the Black Sea.
The Razoni, which is carrying 26,000 tonnes of grain, is heading for Istanbul before sailing on to Lebanon.
The sailing was made possible after Turkey and the United Nations brokered a grain-and-fertiliser export agreement between Russia and Ukraine last month.
Ukraine's Foreign Minister Dmytro Kuleba called it "a day of relief for the world", especially for countries threatened by food shortages and hunger because of the disrupted shipments.
"The first grain ship since #RussianAggression has left port," Infrastructure Minister Oleksandr Kubrakov said. "Today Ukraine, together with its partners, makes another step to prevent world hunger."
Moscow also described the sailing as a positive move. Kremlin spokesman Dmitry Peskov told reporters that the departure from Odesa was ""very positive, a good opportunity to test the effectiveness" of the Istanbul agreements".
"Let's hope that the agreements will be implemented by all parties and that the mechanisms will work effectively," he added.
The European Commission also heralded "a welcome first step towards mitigating the global food crisis, which was enhanced by Russia's illegitimate aggression".
Its comments also included criticism of the Russian blockade. A spokesperson referred to "the blockage of Ukrainian ports, in addition to mining, destroying the fields in Ukraine, destroying the silos in Ukraine, burning the grain and wheat or looting and trying to sell it on behalf of Russia".
"We look forward to the implementation of the whole deal and the resumption of Ukrainian exports to... customers all around the world. But they need it because the negative consequences of Russia's aggression against Ukraine and blockage of Ukrainian ports are affecting the most vulnerable people in Africa, in Asia and in Middle East."
Among others to praise the grain ship's departure were NATO Secretary General Jens Stoltenberg, and the United Nations, which said that Secretary General Antonio Guterres hoped the shipments would “bring much-needed stability and relief to global food security".
Turkey's defence ministry confirmed the ship's departure earlier on Monday.
"It was agreed for the Sierra Leone-flagged cargo ship named Razoni, which is loaded with corn, to depart from the Odesa port at 0830 in the morning (0530 GMT) on Aug 1 to go to Lebanon," the ministry said.
"Deployment of other ships are planned within the scope of the determined corridor and method" as part of the July 22 agreement, it added.
The ministry added the ship is expected to reach Istanbul on Tuesday, where it will be inspected, before being allowed to proceed to Lebanon.
In July, Turkey and the United Nations brokered a deal with Russia and Ukraine designed to help relieve a global food crisis caused by blocked Black Sea grain exports.
It was the first major deal between the warring sides since Russia's February invasion of its neighbour and comes as global food prices have soared, and people in some of the world's poorest countries are facing starvation.
Kyiv and Moscow signed two identical but separate documents at the request of Ukraine, which refused to initial any document with Russia.
Under the agreement, "safe corridors" allow the movement of cargo ships in the Black Sea, which "both sides have committed not to attack," said a UN official who requested anonymity.
Negotiators abandoned the idea of clearing the Black Sea of mines -- mainly laid by the Ukrainians to protect their coastline. "Clearing mines would have taken too long," the UN said, adding that "Ukrainian pilots" would clear the way for cargo ships within Kyiv's territorial waters.
But the deal was put in jeopardy within hours of being signed when Russia bombed the Ukrainian port of Odesa. And more recently a Russian strike killed one of Ukraine's richest businessmen who worked in grain exports - with Kyiv calling it a targeted killing.