The teams - seeded third and fourth respectively - occupy the top two spots in Group B, which also features Belgium and Bosnia-Herzegovina, and are yet to taste defeat during the current campaign.
Indeed, Israel have won all three of their fixtures so far, but former Wales manager John Toshack is confident Chris Coleman's men - who have picked up two wins and two draws - will eventually qualify for a first major tournament since 1958.
"I really do feel this is our time," Toshack is quoted as saying by BBC Sport. "I think Chris has been in there long enough and he knows what he's got and he knows how best to go about it.
"Israel away from home won't be easy. It will be a tough, difficult game."
Saturday's fixture will see Wales captain Ashley Williams rack up his 50th cap, having made his first appearance in 2008 before joining Swansea City from Stockport County.
"It has been everything I've ever wanted - and more - in my career," he said earlier this week. "To actually reach 50, it's such a big milestone. There have probably been better players than me who haven't got there.
"We all know how big this game [against Israel] is. None of us will be playing it down.
"With how close the group is, we're very confident to go anywhere and get a result and we're not afraid to say that anymore."
Williams could come up against a familiar face in the shape of Maccabi Haifa striker Itay Shechter, who spent the 2012-13 season on loan at Swansea.
Shechter says his family still has a soft spot for Wales and that he is daunted by the prospect of coming up against former skipper Williams.
"When I had to leave Swansea my wife was crying," he told the South Wales Evening Post. "It was good for me, much better than Germany [where he played for Kaiserslautern]. It was a good place for my family.
"It will be hard to play against Ashley because he is one of the best central defenders in the Premier League."
One of the keys for Wales will be how Gareth Bale responds following fierce criticism of his performances for club side Real Madrid - the attacker is likely to be a central figure in what is arguably Wales' biggest fixture since losing a Euro 2004 play-off against Russia in 2003.
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