The Arleigh Burke-class destroyer left its port in Souda Bay, on the northwest coast of Greece, to conduct drills in the Black Sea with Romanian and Bulgarian forces.
Lt. Shawn Eklund, a Navy spokesman, told Stars and Stripes the deployment wasn't related to Russian military activity in Ukraine.
"Truxtun's operations in the Black Sea were scheduled well in advance," he said in an interview published Thursday.
The Russian navy's Black Sea fleet operates from the Ukrainian peninsula of Crimea and regional Russian ports.
Russian President Vladimir Putin said he reserved the right to use force in the region to protect Russia's strategic interests, but only as a last resort.
Ukraine, a former Soviet republic, descended into chaos in November when now ousted President Viktor Yanukovych, a Kremlin ally, suspended efforts to sign free trade and association agreements with the European Union. Putin's administration said it doubted the legitimacy of Ukraine's new leaders.
U.S. President Barack Obama said he wouldn't tolerate Russian aggression in the region, but recognized Ukraine's historic ties to Moscow.