The three-times weekly service to Ben Gurion will get under way on May 26, the airline has announced.
Flights will be operated by Boeing 737-800 aircraft featuring two cabins, economy and business.
Ben Gurion airport is situated between Israel’s major cities of Tel Aviv and Jerusalem, and opens up the country’s beach resorts.
The launch supports Israel’s Two Sunny Cities, One Break campaign, which highlights the country’s “non-stop nightlife, culture, sandy beaches and year-round sunshine”.
Michael Strassburger, El Al vice-president commercial and industry affairs, said: “El Al will significantly expand its roster of destinations in Europe in 2019.
“Manchester has a large Jewish community and is a centre of business and tourism. This is good news not only for Israeli consumers; we also anticipate carrying thousands of tourists to Israel on this new route.”
Yariv Levin, Israeli minister of tourism, added: “With more carriers flying to Israel, it is clear there is ever-increasing demand to visit our country. We look forward to showing everything we have to offer to visitors in 2019”.
Introductory fares lead in from £199 for a one-way economy seat with hand baggage, and £289 return. Return business class fares lead in from £929.
Tickets are on sale now for travel from May 26 to July 11 and September 1 to September 24.