Beresheet, which means "Genesis" in Hebrew, lifted off at 8:45 pm (0145 GMT Friday) atop a Falcon 9 rocket from the private US-based SpaceX company of entrepreneur Elon Musk. After detaching from the launcher, the spacecraft will orbit the Earth for a few months before landing on the moon in late April.
The Beresheet spacecraft will measure magnetic fields on the moon, data which will be transferred to the Weizmann Institute to help scientists study how the moon was formed billions of years ago.
The 585kg lander will make its way to the Moon under its own power and is expected to arrive in orbit on 4 April before heading to a soft landing on 11 April.
The $100 million (NIS 370 million) spacecraft is a joint venture between private companies SpaceIL and Israel Aerospace Industries, funded nearly entirely by private donations from well-known Jewish philanthropists, including South African billionaire Morris Kahn, Miriam and Sheldon Adelson, Lynn Schusterman, and others. "This is a big milestone".
The Falcon 9 rocket that brought Beresheet into space also deployed a large geo-communication satellite and other equipment for the US Air Force.
Israeli Prime Minister Benjamin Netanyahu watched the takeoff of the unmanned mission live in Israel at the control center of Israel Aerospace Industries.
A flight path directly from Earth to the moon would cover roughly 240,000 miles (386,242 km), but Beresheet will follow a more circuitous route.
So far, only Russian Federation, the United States and China have made the 384,000-kilometer (239,000-mile) journey and landed spacecraft on the Moon. The lander will also carry a time capsule, which contains a "Lunar Library". "This is a historic step for all nations and commercial space as we look to extend our collaborations beyond low-Earth orbit and on to the Moon", said in a statement NASA Administrator Jim Bridenstine.
Spacecraft from several countries, including India's Moon Impact Probe, Japan's SELENE orbiter and a European Space Agency orbital probe called SMART 1, have intentionally crashed on the lunar surface.
SpaceIL has no plans for future explorations of its own beyond Beresheet and "will not continue after this mission", Harel said.