From 1938 to 1947, Ponomarenko was the First Secretary of the Communist Party of Belorussia, and from 1944 to 1948, also the Chairman of the Council of Ministers. During World War II, he led Communist partisan units within Nazi-occupied Belarus. He clashed with the Polish underground and gave orders for his troops to disarm them. This led to a number of deaths.
From 16 October 1952 until 6 March 1953, Ponomarenko was a member of the Politburo of the Communist Party of the Soviet Union. He was made First Secretary of the Communist Party of the Kazakh SSR in 1954 before becoming the Soviet ambassador to Poland between 1955 and 1957.
Ponomarenko also taught diplomacy and assisted in the creation of the National Jazz Orchestra in Minsk.