Arleigh Burke's designers incorporated many lessons learned by the Royal Navy during the Falklands campaign and from the Ticonderoga-class guided-missile cruisers.

As is often the case with new ship classes, U.S. Navy officers and shipyard engineers encountered a number of problems with some shipboard systems that required the attention of the warship's design and production agencies.

An additional phase of testing was added to verify the effectiveness of the modifications made to these systems—modifications incorporated into later destroyers of the Arleigh Burke class.

During her second deployment in 1995, Arleigh Burke steamed in the Mediterranean Sea as the "Red Crown" in support of the No-Fly Zone over Bosnia and Herzegovina.

During her fourth cruise in 2000–2001, Arleigh Burke saw service in the Mediterranean and Red Seas and in the Persian Gulf, enforcing United Nations sanctions against Iraq and conducting exercises with allied naval partners.

During this wartime cruise, Arleigh Burke fired Tomahawk missile strikes against targets in Iraq, escorted merchant ships and naval auxiliaries through geographic choke points, and carried out "leadership interdiction" operations in the northern Arabian Sea.

In May 2007, Arleigh Burke ran what the Navy called a "soft aground" off Cape Henry Light at the entrance to the Chesapeake Bay.

The ship represented the United States during a port visit to the island nation of Seychelles where they played a role in securing a status of forces agreement between the two countries.

[8] On 23 September 2014, Arleigh Burke took part in the 2014 military intervention against ISIS, firing Tomahawk missiles on targets in Syria while the ship was in the Red Sea.

In 2019, she entered General Dynamics NASSCO's shipyard in Norfolk, Virginia, for continued work towards modernization for ballistic missile defense.

[10] In March 2021, during the COVID-19 pandemic, Arleigh Burke transited the Atlantic Ocean and conducted a home port shift to Rota, Spain, joining the Forward Deployed Naval Forces in Europe as part of Destroyer Squadron 60.

Port calls included Tallinn, Estonia; Helsinki, Finland; Gdynia, Poland; Varna, Bulgaria; Constanta, Romania; and Golcuk, Turkey.

The Battle "E" recognizes the top ship in each squadron and is awarded for demonstrating sustained superior performance, operational effectiveness, and continuous readiness.