Dos Santos rose through the MPLA ranks in 1974 when he was named second-in-command of telecommunications services for the MPLA Second Politico-Military Region in Cabinda. He was also chosen as a member of the Provisional Readjustment Committee for the Northern Front. In September of the same year, he was appointed to the MPLA Central Committee and was ranked fifth on the Political Bureau.
At the formation of the first MPLA government in November 1975, dos Santos was named chairman of the MPLA and minister of foreign affairs. He moved on to the position of coordinator of the MPLA Foreign Relations Department. He was central committee secretary for several departments, including education, culture and sport, national reconstruction, and economic development and planning. In 1978 he was named minister of national planning, first deputy prime minister, and head of the MPLA's National Planning Committee. President Neto went to the USSR for medical treatment in September 1979, and before leaving he
designated dos Santos to take charge of the government during his absence. Neto died in Moscow on 10 September 1979. Thereupon, the central committee "unanimously and by strong acclamation" elected dos Santos to succeed Neto as president of the MPLA. He took office as president of the People's Republic of Angola on 21 September 1979.