The reshuffle at the helm for the Wales' national side is a result of the temporary departure of Warren Gatland, Rob Howley and Shaun Edwards to South Africa to coach under Ian McGeechan on the British and Irish Lions tour this summer.
Holley's role in the Wales set-up has been endorsed by the Ospreys region, where he will return on completion of his duties in Chicago and Toronto.
"It's a great honour to be able to coach at international level and to coach your own national team is even greater," said Holley.
"I am very much looking forward to the challenges ahead, my immediate focus is to integrate myself as part of this coaching team as quickly as possible and to ensure that I do what I can to ensure this is a successful tour.
"The life of a rugby coach is a challenging and demanding one with many pressures but it is those pressures which are also the making of you as a coach and this latest challenge is one that I am very much relishing."
Andrew Hore, Ospreys Elite Performance Director, said: "I'd like to congratulate Sean on this appointment on behalf of everybody at the Ospreys. As a young Welsh coach, to be handed the opportunity to work with the national team is the ultimate accolade. His appointment is richly deserved and I have no doubt that the experience that he will get during this tour will stand both Sean and the Ospreys in good stead in the long term.
"Sean is one of the brightest young Welsh coaches, and everybody in the region can take great satisfaction from this news. It is our goal now to ensure that we continue to produce more exciting, Welsh coaches in the future through the coaching development programe we are introducing, which will, in turn, help to secure the long term sustainability of rugby in the region ."