The Royal Navy has confirmed that HMS Diamond is due to leave the city at noon.
She will join NATO forces, alongside HMS Trent, in the eastern Mediterranean amid growing tensions between Russia and Ukraine.
A Ministry of Defense spokesman said: ‘HMS Diamond is due to leave Portsmouth at 12 noon today.
The Portsmouth ship HMS Trent carries out patrols in the eastern Mediterranean with NATO …
“It will support a NATO task force in the Eastern Mediterranean region.”
The Type 45 destroyer was due to leave Portsmouth Naval Base last night before the departure was postponed to 7am this morning, but was delayed due to weather.
The Portsmouth-based warship, HMS Trent, has begun patrolling the eastern Mediterranean, with allies from Canada, Italy, Spain and Turkey accompanying her.
The UK is also sending additional tanks and vehicles to Estonia, while doubling the number of troops in the country.
Four Typhoon jets have landed in Cyprus, aiming to patrol the skies of Eastern Europe with NATO allies.
More than 100,000 Russian troops have massed on the Ukrainian border, although the Kremlin denies any prospect of an invasion.
Defense Secretary Ben Wallace said: “Alongside our NATO allies, we are deploying troops and assets on land, at sea and in the air to bolster Europe’s defenses in response to the buildup of forces Russian military on the Ukrainian border.”
Last Friday, the Foreign, Commonwealth and Development Office advised all British nationals in the country to leave immediately as trade travel is still available.
At a press conference last week between Boris Johnson and NATO Secretary General Jens Stoltenberg, Mr Johnson said Europe was in the grip of its deepest security crisis in decades.
The Prime Minister warned of “serious bloodshed” if an invasion took place.
Dr Paul Flenley, a lecturer in politics at the University of Portsmouth and an expert on Russian foreign policy, does not see progress in the diplomatic talks.
He told The News: “There really is a stalemate.
“From the Western point of view, there will be no change to Ukraine’s invitation to join NATO, which is one of Vladimir Putin’s demands.
“There will also be no withdrawal of NATO troops from former Soviet states.”