He won the 2000 Ghanaian general election after defeating National Democratic Congress (NDC) candidate John Atta Mills by earning 56.9% of the votes.

Kufuor ran for re-election in 2004, winning again against John Atta Mills, and served two full terms.

In the first round of voting, held on 7 December 2000, Kufuor came in first place with 48.4%, while John Atta-Mills, the NDC candidate, came in second with 44.8%.

[13] The National Reconciliation Commission was formed in 2004 to investigate human rights abuses committed by previous Ghanaian military juntas and unconstitutional governments.

[21] This included the addition of the Accident and Emergency Centre at the Komfo Anokye Teaching Hospital, which became the largest in Ghana upon completion.

He institutionalised the capitation grant for school children at the basic level as each student was entitled to $2 for cultural sports and development.

[25] President Kufuor obtained a record $500 million grant from the US's Millennium Challenge Account for economic development.

Kufuor was re-elected in presidential and parliamentary elections held on 7 December 2004, earning 52.45% of the popular vote in the first round.