Amos de-Shalit was born in Jerusalem in the British Mandate of Palestine (now Israel). He grew up in Tel Aviv and graduated from Gymnasia Balfour. In 1949, de-Shalit earned his master's degree in physics at the Hebrew University of Jerusalem under the guidance of Giulio Racah. During the 1947–1949 Palestine war, he served in the IDF Science Corps. De-Shalit and his fellow students wrote a letter to Israeli Prime Minister David Ben-Gurion to point out the vital importance of nuclear physics for Israel's future. In 1951, he earned his doctorate from the ETH Zurich in Switzerland.