She sang her biggest hits, old and new, to a raucous crowd near Tel Aviv on Thursday.
Madonna, who follows a form of Jewish mysticism called Kabbalah, has long claimed a special bond with Israel. She draped herself in an Israeli flag during her last performance in Israel in 2009.
After her show near Tel Aviv, the "MDNA" tour moves to Abu Dhabi and includes stops in Istanbul, Cleveland and Buenos Aires.
Her last tour grossed more than $400 million.
The Associated Press contributed to this report.