Zijlstra studied Economics at the Rotterdam School of Economics obtaining a Master of Economics degree and worked as a researcher and lecturer at his alma mater before finishing his thesis and graduated as a Doctor of Philosophy in Public economics and worked as a professor of Public economics at the Free University Amsterdam from October 1948 until September 1952. After the election of 1952 Zijlstra was appointed as Minister of Economic Affairs in the Cabinet Drees II taking office on 2 September 1952. After Party Leader Jan Schouten announced his retirement Zijlstra was selected his successor as Leader on 23 April 1956. For the election of 1956 Zijlstra served as "Lijsttrekker" (top candidate) and was elected as a Member of the House of Representatives and Parliamentary leader taking office on 3 July 1956. Following a cabinet formation Zijlstra continued as Minister of Economic Affairs in the Cabinet Drees III and stepped down as Leader and Parliamentary leader on 3 October 1956. The Cabinet Drees III fell on 11 December 1958 and was replaced by the caretaker Cabinet Beel II with Zijlstra retaining his position and also becoming Minister of Finance taking office on 22 December 1958. For the election of 1959 Zijlstra again served as "Lijsttrekker". Following a cabinet formation Zijlstra continued as Minister of Finance in the Cabinet De Quay. In September 1962 Zijlstra announced that he wouldn't not stand for the election of 1963 and declined to serve in new cabinet. Zijlstra returned as a distinguished professor of Public economics at the Free University Amsterdam and was elected as a Member of the Senate after the Senate election of 1963 taking office on 25 June 1963 serving as a frontbencher and spokesperson for Finance. Zijlstra also served as director of the Abraham Kuyper Foundation from August 1963 until November 1966.