Wilson joined Harlequins in the summer of 2023 and led the club to the Champions Cup semi-finals in his first campaign.
He said he was “hugely proud” of blooding young talent and will lead Quins for the last time in Friday’s opening game of the season at Newcastle Red Bulls in the Prem Rugby Cup.
Harlequins have confirmed the coaching group of Nick Evans, Jason Gilmore, Gerard Mullen and, another potential Wales target, Adam Jones will take charge for the “short-term” alongside general manager Andy Sanger.
Chief executive Laurie Dalrymple 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.”