She has a raised forecastle, a transom stern, a bulbous bow, an extended deckhouse with a forward bridge, and a helicopter-landing deck with a flight-control facility.

[5][6] Like most USNS ships, mariners from the US Navy's Military Sealift Command are responsible for navigation, propulsion, and most deck duties on board.

[7] Mercy departed San Diego in 2006 as the inaugural deployment of Pacific Partnership, an ongoing Civic Assistance mission designed to "Prepare in Calm to Respond in Crisis".

Mercy departed San Diego on 14 April 2008 for Pacific Partnership 2008, a four-month humanitarian and civic deployment in Southeast Asia and Oceania.

Partners participating in the mission included the nations of Australia, Canada, Chile, Japan, South Korea, New Zealand, and Portugal, as well as several non-governmental organizations.

In an effort to further expand the scope of the mission of "Preparing in Calm to Respond in Crisis", many more man hours of Subject Matter Expert Exchange (SMEE) with host nations, Veterinary Care, and construction projects were performed compared to past Mercy deployments, building the capacity of host nations to respond to regional disasters in a coordinated manner.

The ship visited Indonesia, the Philippines, Vietnam, and Cambodia carrying personnel not only from the Department of Defense, but also 13 partner nations and 28 non-governmental organizations.

[11] The National Conflict Resolution Center honored the master and crew of hospital ship USNS Mercy with its 25th annual Peacemaker Award for her participation in Pacific Partnership (2012).

[12] In mid-November 2013, Mercy was ordered to activate for Operation Damayan, the relief effort in response to the devastation caused by Typhoon Haiyan, which struck the Philippines on 7 November 2013.

[13][14] The US Navy announced that Mercy would be participating in RIMPAC 2014, a large multi-national naval exercise involving ships and personnel from 23 countries.

Focusing on Subject Matter Expert Exchanges and Community Health Engagements, Pacific Partnership 15 looks to continue the mission of helping nations in the region "Prepare in Calm to Respond in Crisis".

[18] The United Seamen's Service at its annual Admiral of the Ocean Sea Awards (AOTOS) event honored the masters and crews of hospital ship USNS Mercy with Special Recognition Mariner's Plaque for her participation in Pacific Partnership (2018).

[27] On 31 March 2020, while Mercy was docked, a Pacific Harbor Line freight train was deliberately derailed by its onboard engineer in an attempt to crash into the ship, but the attack was unsuccessful.

[30] The train came to a stop approximately 750 feet (230 m) from the ship after destroying several barriers and suffered a substantial fuel oil leak requiring cleanup from fire fighters and hazardous materials personnel.