During the early 1930s Eyskens was chief of staff of CVP ministers Edmond Rubbens and Philip Van Isacker.
In 1939 Eyskens was elected to the Belgian Chamber of Representatives.
He was steadily re-elected (in 1946, 1949, 1950, 1954, 1958 and 1961) and served until 1965.

In 1945 and between 1947 and 1949 he was Minister of Finance.
On 11 August 1949 he became Prime Minister of Belgium in a coalition (Eyskens I) between Christian-democrats and liberals.
His cabinet fell in June 1950 over the constitutional crisis caused by King Leopold III's actions during the Second World War.
In the short lived government of Jean Duvieusart (June–August 1950) Eyskens was Minister of Economic Affairs.

Between 26 June 1958 and 6 November 1958, Eyskens led a minority government which was the most recent government of Belgium (Eyskens II) not to be a coalition government.
On 6 November, Eyskens formed a coalition government with the liberals (Eyskens III) which remained in power until 3 September 1960.
On 3 September 1960 he formed his third government (Eyskens IV), again a coalition with the liberal party.
This government fell on 25 April 1961 over the Unitary Law (which raised the fiscal pressure by 7 billion Belgian francs, cut spending in education and the military, and reformed unemployment benefits and government pensions) and had caused large-scale strikes.
During these years he also had to deal with the School War and the independence of the Belgian Congo.

In the general election of 1965 Eyskens was elected to the Belgian Senate (re-elected in 1968 and 1971).
In the government led by Pierre Harmel (1965–1966) he again served as Minister of Finance.
Student unrest and questions of discrimination against the ethnic Flemish population brought down the Belgian government in February 1968.
On 17 June 1968, Gaston Eyskens formed his fifth government (Eyskens V); this time a centre-left coalition between the Christian Democrats and the Socialists.
On 20 January 1973, he formed his sixth and last government (Eyskens VI), again a coalition with the Socialists.

His last two governments were plagued by linguistic troubles regarding the split of the old bilingual Catholic University of Leuven into a Dutch-language university (the Katholieke Universiteit Leuven), which stayed in Leuven and a French-language university which moved to Louvain-la-Neuve and became the Université catholique de Louvain and the start of the process of changing Belgium from a unitary state into a federation with the creation of the Communities.
Upon the fall of his last government Gaston Eyskens retired from politics.
 He died in Leuven.
During the early 1930s Eyskens was chief of staff of CVP ministers Edmond Rubbens and Philip Van Isacker. In 1939 Eyskens was elected to the Belgian Chamber of Representatives. He was steadily re-elected (in 1946, 1949, 1950, 1954, 1958 and 1961) and served until 1965.
In 1945 and between 1947 and 1949 he was Minister of Finance. On 11 August 1949 he became Prime Minister of Belgium in a coalition (Eyskens I) between Christian-democrats and liberals. His cabinet fell in June 1950 over the constitutional crisis caused by King Leopold III's actions during the Second World War. In the short lived government of Jean Duvieusart (June–August 1950) Eyskens was Minister of Economic Affairs.
Between 26 June 1958 and 6 November 1958, Eyskens led a minority government which was the most recent government of Belgium (Eyskens II) not to be a coalition government. On 6 November, Eyskens formed a coalition government with the liberals (Eyskens III) which remained in power until 3 September 1960. On 3 September 1960 he formed his third government (Eyskens IV), again a coalition with the liberal party. This government fell on 25 April 1961 over the Unitary Law (which raised the fiscal pressure by 7 billion Belgian francs, cut spending in education and the military, and reformed unemployment benefits and government pensions) and had caused large-scale strikes. During these years he also had to deal with the School War and the independence of the Belgian Congo.
In the general election of 1965 Eyskens was elected to the Belgian Senate (re-elected in 1968 and 1971). In the government led by Pierre Harmel (1965–1966) he again served as Minister of Finance. Student unrest and questions of discrimination against the ethnic Flemish population brought down the Belgian government in February 1968. On 17 June 1968, Gaston Eyskens formed his fifth government (Eyskens V); this time a centre-left coalition between the Christian Democrats and the Socialists. On 20 January 1973, he formed his sixth and last government (Eyskens VI), again a coalition with the Socialists.
His last two governments were plagued by linguistic troubles regarding the split of the old bilingual Catholic University of Leuven into a Dutch-language university (the Katholieke Universiteit Leuven), which stayed in Leuven and a French-language university which moved to Louvain-la-Neuve and became the Université catholique de Louvain and the start of the process of changing Belgium from a unitary state into a federation with the creation of the Communities. Upon the fall of his last government Gaston Eyskens retired from politics.  He died in Leuven.
Gaston Eyskens