Humphreys will leave the Ospreys when his current contract expires at the end of the season.
Former Wales captain Humphreys, who joined the region in the summer of 2005, will exit the Liberty Stadium next month after eight years with the Ospreys to pursue other opportunities in the game.
Appointed shortly after the region had claimed its first Celtic League title, during his time as an Osprey Humphreys helped the team towards a further three league successes and EDF Energy Cup Final win over Leicester at Twickenham in 2008.
He played a part in the development of a host of international class forwards who have come through the pathway at the region, with the Ospreys now renowned as a centre of excellence in terms of forward development.
Humphreys said: "It's with a heavy heart I'm confirming that I am leaving the Ospreys after eight years. I would like to take this opportunity to thank the Ospreys for everything that they have done for me. They gave me the opportunity to coach at the top level and have stuck by me through a lot of change and upheaval.
"I'm extremely proud of the trophies that we have won but I am even more proud of the players that we have developed to represent Wales and the Lions. I feel extremely fortunate to have coached the calibre of player that I have had at my disposal and to see them grow to go on to play international rugby."