In 1925 he was a delegate at the Zionist Congress, where he was elected onto the executive committee. In the same year he immigrated to Mandate Palestine. In 1928 he was elected onto the Central Committee of the Hapoel HaMizrachi movement, and also served as a member of the World Mizrachi committee.
In 1936 he was elected as a member of the Zionist Directorate and a Director of the Aliyah department of the Jewish Agency, a role he filled until 1948. In 1938 he was sent on a special mission to try and save Jews in Austria following the takeover by Nazi Germany.
In Israel's first elections in 1949, Shapira won a seat as a member of the United Religious Front bloc, an alliance of Agudat Israel, Agudat Israel Workers, Mizrachi and his Hapoel HaMizrachi party. He was reappointed to his previous ministerial posts, and also became Minister of Internal Affairs.
After the 1951 elections in which Hapoel HaMizrachi ran as an independent party, Shapira was appointed Minister of Internal Affairs and Minister of Religions. Following a cabinet reshuffle in 1952, he lost the Internal Affairs portfolio, but was appointed Minister of Welfare instead. Another reshuffle in 1955 saw him regain the Internal Affairs portfolio.
The 1955 elections saw Mizrachi and Hapoel HaMizrachi run as a combined bloc, the National Religious Front, which later became the National Religious Party (NRP). Shapira was reappointed Minister of Religions and Minister of Welfare. In 1957 he was seriously injured by a hand grenade thrown into the Knesset by Moshe Dwek, but survived. He and all other NRP ministers resigned from the cabinet in July 1958, marking the only spell he spent out of office during his time in Israel.