Mansholt came from a socialist farmer's family in the Dutch province of Groningen. Both his father and grandfather were supporters of socialist forefighters such as Multatuli, Domela Nieuwenhuis and Troelstra. His father, Lambertus H. Mansholt, was a delegate for the socialist SDAP party in the Groningen provincial chamber. His mother, Wabien Andreae, daughter of a judge in Heerenveen, was one of the first women to have studied Political Science. She organised political meetings for other women, usually in their own homes. Mansholt attended the HBS-school in Groningen and after that went to Deventer, to the School of Tropical Agriculture, where he studied to become a tobacco farmer.
He moved to Java in the Dutch East Indies, nowadays Indonesia, and started to work in a tea plantation. He returned to the Netherlands in 1936, unhappy with the colonial system. He wanted to become a farmer and moved to the Wieringermeer, a polder, reclaimed in 1937. There he started his own farm.
There he became a member of the SDAP, as a secretary of the local party. He had several public functions for the SDAP in Wieringermeer, including that of acting mayor of the Wieringermeer community. In the years of the Second World War he was an active member of the Resistance. He helped people who were in acute danger to hide in the Wieringermeerpolder; he organised clandestine food distributions for the western provinces. Immediately after the war, in June 1945, socialist PvdA Prime Minister Schermerhorn asked him to take a seat in his cabinet as minister of Agriculture, Fishery and Food Distribution. He was the youngest member of a cabinet, aged only 36.
He was a member of 6 cabinets in total: Schermerhorn-Drees in 1945; Beel in 1946; Drees-Van Schaik in 1948, and another three Drees administrations: 1951, 1952 and 1956. In 1958 he became one of the Commissioners of the new European Commission. He was Commissioner for Agriculture, modernising European Agriculture and vice-president of the institution. He became President of the European Commission on 22 March 1972 (Mansholt Commission) and continued in that position until 5 January 1973. It was around that time he was heavily under the influence of Club of Rome.
In 1954 the parliamentary debate about the budget for the Department of Agriculture was postponed: the Minister was ice-skating the 200 kilometer long Elfstedentocht in the Dutch province of Friesland. He skated this famous ice-skating race twice in his life.
He married Henny J. Postel in 1938, and they had two sons and two daughters. Sicco lived his last years in on an old historic farm in the quiet village of Wapserveen in the province of Drenthe (north-east Netherlands). He died there on 30 June 1995. Their daughter Lideke died in 1995, aged 53.