While taking part in FTM-12 exercise on 22 June 2007 in Hawaiian waters, Méndez Núñez became the Spanish Navy's first ship to detect and track a ballistic missile.

[4] On 21 April 2008, while part of the Royal Navy's HMS Illustrious Combat Group in the Red Sea,[5] Méndez Núñez was ordered to move to Somalia's coast in support of the tuna vessel Playa de Bakio, which had been seized by Somali pirates.

On 11 September 2009 Méndez Núñez, her sister ship Álvaro de Bazán, and the Santa María-class Navarra, and their respective air units, carried out exercises with the students of the Naval School in the estuary of Pontevedra.

[9] Between 21 and 30 June 2010 Méndez Núñez and the Spanish oiler Patiño took part in Exercise Swordfish in Portuguese waters, together with units from Portugal, Italy and France.

[11] Later that day Méndez Núñez participated in the exhibition A safe maritime environment for the XXI century held in Vigo next to the vessels Galicia, Juan Sebastián Elcano and Chilreu.

After receiving assistance from Méndez Núñez, the Royal Grace continued her voyage escorted by the Spanish patrol ship Rayo, bound for the port of Salalah in Oman.

[21] At the beginning of June, Méndez Núñez was incorporated into Standing NATO Maritime Group 1 as a command vessel, relieving Álvaro de Bazán.

[28] On 5 September 2019, Méndez Núñez made the historic port-visit to the Philippines, making it the 1st Spanish Navy vessel to do so, since the Battle of Manila Bay during the Spanish–American War in 1898.