The deployment was conceived following the 2004 Indian Ocean earthquake and tsunami, as a way to improve the interoperability of the region's military forces, governments, and humanitarian organisations during disaster relief operations, while providing humanitarian, medical, dental, and engineering assistance to nations of the Pacific, and strengthening relationships and security ties between the nations.

[1][2] The first such deployment was conducted in 2006, based aboard the hospital ship USNS Mercy, and included partner nations such as Australia (which has contributed consistently since), and non-government organizations.

[3] In 2007, the Pacific Fleet prepared another deployment, this time based aboard the amphibious warfare ship USS Peleliu.

Pacific Partnership provided humanitarian and engineering assistance by visiting the Republic of the Philippines, Vietnam, Timor-Leste and Papua New Guinea.

The USNS Mercy (T-AH 19) and her crew of U.S. military, partner-nation representatives and non-governmental organizations (NGO) arrived in Chuuk, Federated States of Micronesia, for the final mission site for Pacific Partnership 2008.

During the 10 days in Micronesia the mission was carried out with the NGO's and in close coordination and partnership with local medical care professionals.

Volunteers from Project Hope and the University of California at San Diego Pre-dental Society worked closely with the U.S. and partner-nation medical personnel.

[6] In addition to USN personnel, resources deployed include personnel and equipment from other branches of the United States Armed Forces, government agencies, non-government organizations, and the militaries of Canada, Singapore, and Spain; ships from the United States Coast Guard, Australia, New Zealand, and Japan; and a helicopter team from France.

[3][8][9] In the first three ports, 21,000 patients were treated, thousands of contact hours of formal Subject Matter Expert Exchanges (SMEEs) were completed, and classrooms and a water catchment system were built.

[6] The 2012 deployment began with the USNS Mercy departing San Diego on 3 May and concluding its last humanitarian/medical mission in Cambodia on 11 August before heading for home port.

[13] In Cambodia 12,679 patients were triaged; three surgical civic assistance programs resulting in 218 surgeries on board hospital ship USNS Mercy (T-AH 19) and at Preah Kossamek military hospital in Phnom Penh; four medical subject matter expert exchanges (SMEEs) on surgeries and medical techniques; three bio-medical repair SMEEs which resulted in 64 equipment repairs; two veterinary civic assistance projects where 1,375 animals received exams and treatments; three engineering civic assistance projects resulting in three new maternity wards.