He was born in Athens in 1899. After graduating from the Law School of the National and Kapodistrian University of Athens in 1918 he joined the diplomatic corps. After completing his doctoral studies (1924 - 1928) in Heidelberg, Weimar Republic Germany, he returned to Greece where he became a professor of law in 1933. In 1940, he was arrested and exiled for opposing the 4th of August Regime under Prime Minister of Greece Ioannis Metaxas. During the Axis occupation of Greece during World War II, Tsatsos participated in the Greek Resistance and then he fled to the Middle East, where the exiled Greek government was seated.

After the end of World War II, in 1945 he returned to Greece and entered politics and became minister for the first time. In 1946, when he decided to participate more actively in the politics of Greece, he resigned from his post at the National and Kapodistrian University of Athens and then he became a member of the Liberal Party. After the formation of the National Radical Union by Constantine Karamanlis, in 1955 he became a member of the party and one of the closest colleagues of Karamanlis, although, ideologically, he was a centrist-liberal and not a conservative.

He served as a member of parliament and in various ministerial positions until the Greek military junta of 1967 - 1974. Under the first premiership of Karamanlis (1955 - 1963) he served for many years as Minister of Public Administration. After the Metapolitefsi (change of regime from dictatorship to the 3rd Hellenic Republic) in 1974, he was elected again as member of the Hellenic Parliament and became Minister for Culture. In 1975, he was elected President of the Republic by the parliament. He retired after serving his five-year term. He died in 1987 in Athens. He was survived by his wife, Ioanna née Seferiádou, the sister of the Nobel laureate poet George Seferis.

Konstantinos Tsatsos served as professor of the philosophy of law from 1933 since 1946, when he entered politics. Since 1962 he was a member of the Greek Academy. His vast writing work includes textbooks of legal theory, surveys on philosophy and history, as well as literary works, poems, essays and translations of ancient Greek and Roman classics. In 1974, he presided over the parliamentary commission that submitted the first draft of the new constitution.