Lloyd Austin was due to meet Netanyahu and Israeli Defence Minister Benny Gantz during the two-day visit, which officials said would include discussions of US arms supplies to Israel, Reuters reported.
Washington has sought to reassure Israel on regional security issues while restarting talks - so far indirect and inconclusive - about a US return to the 2015 nuclear deal between major powers and Iran that the previous Trump administration quit.
Israel has long been critical of the deal, saying it would not be bound by diplomacy.
Israel and Iran have in recent weeks reported sabotage to their ships at sea. Syria has accused Israel of airstrikes on its territory.