Yitzhak Cohen was born in Ashkelon, Israel in 1951.
He served in the IDF and was educated in a Talmudic college.

Cohen is a former Deputy Mayor of Ashkelon and a former Secretary-General of El Hama'ayan, the Shas-affiliated educational institution. He is married and has ten children.

Yitzhak Cohen has been a member of the Knesset for the Shas party since 1996. He has served as a member of the Knesset House, Finance, Foreign Affairs and Defense, Labor and Social Affairs Committees.

Yitzhak Cohen served as Minister of Religious Affairs from July 1999 until his resignation in July 2000. He served as Deputy Minister of Finance from May 2001 until February 2003. He served as Minister without Portfolio, responsible for the religious councils from May 2006 until March 2009.

In April 2009 Yitzhak Cohen was appointed Deputy Minister of Finance, serving until February 2013.  In May 2015 he was again appointed Deputy Minister of Finance.