On 21 December 2006, he became the NDC's candidate for the 2008 presidential election, winning his party's ticket by an 81.4% result (1,362 votes), far ahead of his opponents, Ekwow Spio-Garbrah, Alhaji Mahama Iddrisu, and Eddie Annan.

The result was a slim lead held by Mills, but due to problems with the distribution of ballots, the Tain constituency, located in the Brong-Ahafo Region, was forced to vote again on 2 January 2009.

John Atta Mills was sworn in as president on 7 January 2009 in a peaceful transition after Akufo-Addo was narrowly defeated.

[18] Muntaka Mohammed Mubarak, the Minister for Sports, resigned on 25 June 2009 following findings of financial impropriety against him by a committee set up by government.

These include William Kwasi Aboah for Interior, Lee Ocran for Education, Fritz Baffour MP for Ablekuma South for Information, Moses Asaga for Employment and Social Welfare, Dominic Azimbe Azumah, MP for Garu - Timpane – Minister of State and Amin Amidu Sulemani, Upper West Regional Minister designate.

[28] This is indicative of prudent fiscal, monetary and other austerity policy measures that characterised his presidency to put the economy in healthy shape.

[32] There was also a huge improvement in Ghana's gross international reserves and foreign direct investments (FDI) highlighting exceptional macroeconomic performance.

[33] The Mills government also implemented the Single Spine Salary system which increased compensation levels of all public sector workers.

[28] Under his governance, Ghana met three out of the four primary convergence criteria for the proposed common currency, Eco of the West African Monetary Zone.

The rebase moved Ghana into middle income status and it placed the country as the third largest in the ranking of GDP per person in West Africa behind Cape Verde and Nigeria.

[42] In order to ensure inter-generational equity because of the "finite nature of resource revenue" as well as financial security for future Ghanaian generations, the Mills government established in 2011, the Ghana Heritage Fund[43] - a sovereign wealth fund generated from petroleum revenue accumulated from the country's oil and gas industry.

In 2009, the Journal of International Affairs at Columbia University featured Mills as one of the "Five Faces of African Innovation and Entrepreneurship" along with South African innovator, Euvin Naidoo and Mo Ibrahim, (founder of Celtel International and Chairman of the Mo Ibrahim Foundation) where he was lauded for his commitment to strengthening Ghana's Electoral Commission, National Media Commission and National Commission for Civic Education and more importantly, transparency in public institutions, particularly in the country's growing oil and gas sector.

The BBC described his presidency as that of "a peacemaker who was never one to make disparaging comments in public" despite intense criticisms and vilification from his political supporters and opponents alike.

[60] From 8–10 August, his body lay in state, and Ghanaian government officials, civil society, traditional leaders, the clergy, the general public and dignitaries such as Côte d'Ivoire's Alassane Ouattara, Liberia's Ellen Johnson Sirleaf, Nigeria's Goodluck Jonathan and Senegal's Macky Sall paid their last respects.

Within this period, a two-night vigil was also held at the forecourt of the State House for cultural and musical performances such as traditional dirges, plays and tribute reading.

"[63] Ahead of religious ceremonies on Friday morning, the officially declared national day of mourning, a helicopter hovered over the area dropping leaflets reading: We want peaceful elections in 2012.

[64] The funeral ended with the release of a hundred white doves into the air to signify the peaceful nature of the departed leader.

[64] After the funeral service, the president's body was taken on a military procession through some principal streets of the Ghanaian capital, Accra and then for burial in a newly created presidential mausoleum located in a bird sanctuary, Geese Park renamed Asomdwee (Peace) Memorial Park along the Marine Drive and next to the old seat of government, the 17th-century Fort Christiansborg, (also known as Osu Castle), which overlooks the Atlantic Ocean's Gulf of Guinea.

[65] As the sitting Commander-in-Chief, Mills was accorded full military honours, steeped in distinct and elaborate traditions, including a slow march by the Ghana Army, a fly-past of Ghana Air Force jets ejecting plumes of smoke in the national colours of red, gold and green, with the Ghana Navy ships also performing ceremonial manoeuvres on the shoreline behind the Independence Square and a 21-gun salute accompanying the playing of the bugle call, Sunset and the Christian hymn, Abide with Me (Eventide), in addition to sounding of the Last Post by military buglers after the casket had been lowered into the grave.

[66] Approximately 700 domestic and foreign media outlets received accreditation from the Ghanaian Ministry of Information to cover the event.

The state funeral for the late president was most likely the largest gathering of people in one place at a single public event in recent or modern Ghanaian history.

Following his death, a press statement from the United Nations Secretary-General, Ban Ki-moon said Mills "will be remembered for his statesmanship and years of dedicated service to his country.

"[69] A White House statement from United States President Barack Obama called Mills a "strong advocate for human rights and for the fair treatment of all Ghanaians, tirelessly working to improve the lives of the Ghanaian people; He helped promote economic growth in Ghana in the midst of challenging global circumstances and strengthened Ghana's strong tradition of democracy"[70] while Prime Minister of the United Kingdom, David Cameron praised Mills as "a tireless defender of democracy in West Africa and across the continent"[71] Furthermore, the Prime Minister of Japan, Yoshihiko Noda lauded Mills for "his exemplary leadership which endeared him to the hearts of many and his contribution to strengthening the relationship between Ghana and Japan.

"[73] In a message of condolence from the Vatican City, Pope Benedict XVI "recalled Mills' years of public service and his dedication to democratic principles and entrusted the late president's soul to the providence of Almighty God"[74] The Secretary General of the Commonwealth of Nations, Kamalesh Sharma eulogised Atta Mills by describing him as "an inspiring leader, a strong advocate and champion of the Commonwealth, and our membership benefited enormously from his active participation in Commonwealth life and his wisdom.

"[77] Liberia's president and 2011 Nobel Peace Prize laureate Ellen Johnson-Sirleaf extended her condolences to Ghanaians, saying the news had "come as a surprise.

[70] Nigeria's  President Goodluck Jonathan said of Mills: "he was a great friend of our country and a firm believer in the shared heritage and common destiny of all Africans.

President Mills and I shared a vision of peace and political stability as well as regional and continental economic integration in pursuit of progress and development, in our individual countries, within the sub-region and in Africa as a whole".