After Kenya gained independence on December 12, 1963, Kenyatta convinced Moi that KADU and KANU should be merged to complete the process of decolonization. Kenya, therefore, became a de facto single-party state. Kenyatta secured the  support of the Kalenjin community by first appointing Moi to be the Minister for Home Affairs in 1964, and then to Vice President in 1967.

As a member of what was considered a minority tribe at the time, Moi was also an acceptable compromise for the major tribes. Moi was elected to the Kenyan Parliament in 1963, from Baringo North. Since 1966, until his retirement in 2002, he served as the Baringo Central MP.

As Mzee Kenyatta’s age advanced, Moi faced opposition from the Kikuyu elite known as the Kiambu Mafia, who would have preferred one of their own to be eligible to be next in line after the exit of the first President. This resulted in an infamous attempt to change the Constitution to prevent the Vice President automatically assuming power in the event of the President's death.

The existence of this succession scheme may have led to dangerous political instability if Kenyatta died, given his advanced age and perennial illnesses. However, Kenyatta withstood the political pressure and safeguarded Moi's position.