The USS Donald Cook took up station in the southern port of Rota from where it will operate as an anti-missile platform and take part in other tasks such as maritime security and NATO deployments, a statement said.
"For the first time, a ship of the United States Navy equipped with the Aegis ballistic missile-defence system is permanently based in Europe" NATO Secretary General Anders Fogh Rasmussen said.
"The arrival of the USS Donald Cook marks a step forward for NATO, for European security, and for transatlantic cooperation," Rasmussen said.
The system is designed to "protect all NATO European populations and territory," the statement said.
Supporters cited a major concern as being the threat to Europe from Iranian missiles, especially if Tehran were to acquire nuclear weapons.
Russia however says the system directly threatens its security and the issue has become a major bone of contention with Washington which in turn insists that Moscow's fears are groundless.
The Aegis ships will operate in tandem with land- and other air- and space-based systems to monitor for possible hostile missile launches and then direct missiles to destroy them.
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