Wilson, 49, departs Quins just two weeks before the Gallagher Premiership season begins, swapping club rugby for a permanent role in Tandy’s backroom staff.
The former Cardiff Blues and Glasgow Warriors boss will take charge of Wales’ line-out and contact areas, having already worked with the squad during their summer tour to Japan.
“This has been a really tough decision for me to make as I have thoroughly enjoyed my time at Quins,” Wilson said.
“But the chance to join Wales and return to international rugby was simply too good an opportunity to turn down.
“Having the opportunity to experience international rugby again for the interim period with Wales this summer in Japan was a huge honour.
“I'm delighted to be able to return on a permanent basis and to be able to work again with Steve and this exciting group of young players.”
Wilson’s appointment marks the beginning of a new era for Wales after a disastrous spell that saw the national side lose 18 consecutive Tests and endure back-to-back Six Nations wooden spoons.
Under Tandy, who officially started his role on 1 September, they will host Argentina, Japan, New Zealand and South Africa this autumn in a bid to restore pride and competitiveness.
Tandy said: “I'm delighted to welcome Danny to the team on a permanent basis.
“I’ve worked with him before when we were both with Scotland, and also during his time at Glasgow Warriors, and he is an outstanding coach.
“This is a really exciting time and I'm grateful to Danny for accepting the challenge to share in this experience. We can't wait to get started together preparing for the autumn.”
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Wilson has strong links with Welsh rugby, having previously coached at Dragons, Scarlets, Cardiff and with the national under-20s.
He was also Scotland’s forwards coach between 2018 and 2020, during which time he worked alongside Tandy.
His experience in both domestic and international rugby is viewed as crucial in helping to rebuild a Welsh side at a crossroads.
His switch comes at a politically charged moment for the Welsh game, with the WRU weighing up whether to cut the four professional clubs – Cardiff, Dragons, Scarlets and Ospreys – down to two.
A final decision is expected by the end of October, shortly before Wilson links up again with the squad for the autumn Tests.
Wilson’s move leaves Harlequins in a difficult position, with their Premiership opener against Bath just 15 days away.
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He joined the London club in July 2023 and guided them to their first Investec Champions Cup semi-final in more than a decade last season.
His final match in charge will be Friday’s Premiership Rugby Cup clash against Newcastle Red Bulls.
“I am hugely proud of the work we've undertaken in the last two seasons to blood the next generation of Quins players, and I know this will stand the club in good stead for the 2025-26 season and beyond,” Wilson reflected.
Quins have announced that their coaching group of Nick Evans (attack), Jason Gilmore (defence), Adam Jones (scrum) and Gerard Mullen (skills), together with general manager Andy Sanger, will share responsibility in the interim.
READ MORE: Steve Tandy . . . The Everyman Coach In The Most Scrutinised Job in Wales
Club chief executive Laurie Dalrymple admitted the timing was not ideal but backed Wilson’s decision to return to Test rugby.
He said: “Whilst we recognise we are close to start of the new Prem campaign, we are confident in our coaching team's ability to step up and deliver, and we are excited to kick off our season.
“Things with the WRU have moved quickly but we have been keen to support this move for Danny, which allows him to return to coaching at international level and also supports him from a personal perspective.”
