With Warren Gatland absent through injury, Howley's first game in charge will be against the Barbarians in a capped match at the Millennium Stadium on Saturday.
There are three debutants in the starting XV including Blues flier Harry Robinson along with Scarlets pair Liam Williams and prop Rhodri Jones while the Ospreys, who defeated Leinster on Sunday, provide nine players to the matchday squad.
While the likes of Jamie Roberts, Sam Warburton and Jonathan Davies are all injured, there is still plenty of experience notably on the bench in the form of 99-cap flanker Martyn Williams.
And Howley is looking for Wales to get the perfect send-off ahead of their summer tour against Australia.
He said: "The Ospreys have been in a rich vein of form and their victory over Leinster last weekend to take the Rabodirect Pro12 title was a boost for the whole of Welsh rugby," said Howley.
"Dan (Biggar) and Andrew (Bishop) have been playing particularly well and we are looking forward to seeing both players in a Welsh shirt again.
"We have picked a side on form, with an eye on bringing players through for the future, but very much with the intention of getting the summer campaign off to a winning start.
"We have an opportunity against the Barbarians to get an important summer series off to a winning start.
"We have momentum from the Six Nations and the Ospreys have added to that with a great win in our domestic competition.
"We are now looking for the next step and a victory on home soil against a formidable Barbarians team before we set off for Australia."
Wales: Liam Williams (Scarlets); Harry Robinson (Blues), Andrew Bishop (Ospreys), James Hook (Perpignan), Aled Brew (Dragons); Dan Biggar (Ospreys), Lloyd Williams (Blues); Rhys Gill (Saracens), Matthew Rees (Scarlets, capt), Rhodri Jones (Scarlets), Alun Wyn Jones (Ospreys), Ian Evans (Ospreys), Josh Turnbull (Scarlets), Justin Tipuric (Ospreys), Ryan Jones (Ospreys)
Replacements: Richard Hibbard (Ospreys), Paul James (Ospreys), Aaron Shingler (Scarlets), Martyn Williams (Blues), Rhys Webb (Ospreys), Adam Warren (Scarlets), Will Harries (Dragons)