UJIA chief executive Doug Krikler is leaving to "explore new opportunities" after eight years with the charity.
His decision to quit had been an "emotional moment" and he was "looking at all options" within and outside the Jewish community. He will remain in the post during the search for his replacement.
Mr Krikler joined UJIA in September 2004, becoming chief executive in 2005. He was previously executive director of the Community Security Trust and director of the Maimonides Foundation, promoting Muslim-Jewish relations.
Under his leadership, UJIA has invested more than £60 million in projects in Israel and £30 million in UK educational ventures.
He has passionately defended using UJIA resources to help impoverished Arab citizens in Israel as part of long-term regeneration of the Galil, in the north of the country. He is co-chair of the new UK Taskforce on issues facing Israeli Arabs and has worked closely on Jewish community involvement in the London Olympics.
Mr Krikler said he was most proud of how UJIA had enabled "British Jews to play a role in the development of Israel. I feel we were able to restore our contribution to what it should be. We've tried to grow UJIA from being a fundraising organisation to one that has very clear strategic objectives, through identifying significant challenges in Israel.
"I wanted to focus on the disparity between the prosperous centre and the peripheral communities in the north and south and the social and economic challenges - like those between secular and religious and between Jews and non-Jews. We are finding ways to respond to those challenges. I'd like to see my successor continue to do that. I hope UJIA will also continue to prioritise Israel education here, for the benefit of the state and the Jewish community."
UJIA chairman Mick Davis said Mr Krikler was "a truly outstanding professional. UJIA has been very fortunate to have someone of Doug's skills and experience at the helm."