Teenager Keelan Giles has been named among the replacements for Saturday's clash.
The uncapped 18-year-old Ospreys wing, who has scored eight tries in five games this season, was called into Wales' autumn Test squad last week.
The other changes include a recall for centre Jamie Roberts, who was dropped to the bench against the Pumas, and opportunities for the likes of Cardiff Blues half-backs Gareth Anscombe and Lloyd Williams, Ospreys prop Nicky Smith and Newport Gwent Dragons lock Cory Hill.
Liam Williams and Leigh Halfpenny, meanwhile, swap positions with Williams moving to full-back and Halfpenny on the wing, with flanker Sam Warburton captaining the team.
Wales Under-20 international Giles' blistering pace and dazzling footwork have led some pundits to compare him with Wales' record international try-scorer Shane Williams.
If he features off the bench, he will become the 11th-youngest Wales international of all-time, and the youngest since Dafydd Howells was capped in Japan three years ago.
Halfpenny, meanwhile, makes his first Wales start as a wing since the 2011 World Cup, and Roberts is reunited with midfield partner Jonathan Davies for a 46th time.
Among those players not involved in the match-day 23 as Wales build towards next week's Cardiff appointment with South Africa are established internationals such as wing George North, fly-half Dan Biggar, prop Gethin Jenkins and lock Luke Charteris.
Elsewhere in the team, Anscombe wins his ninth cap, but it will be a first start at fly-half, and Hill makes a full Test debut after going on as a replacement against Australia 12 days ago.
Howley said: "We have made a number of changes, but have named a very experienced side.
"Continuity and momentum is important, hence keeping the likes of Alun Wyn (Jones), Jon Davies and Sam (Warburton) in the side, but it is also an opportunity for players who were disappointed against Australia to start, and for players who have been pushing on selection.
"We have made a change with Liam (Williams) moving to full-back and Leigh (Halfpenny) on to the wing. Leigh has done well at full-back, but we are giving an opportunity to Liam.
"Leigh has played on the wing before - they have trained well there - and we want to have a look at what this option gives us.
"Japan are a much-changed side from the (2015) Rugby World Cup, but (head coach) Jamie Joseph is developing his team, and their recent performances echo the dangers of the World Cup with their ability to move the ball wide early. They are a great counter-attacking team.
"It's important we look at our game and are clinical in what we want to do this weekend."
Wales are set for their biggest crowd of the autumn series so far on Saturday, with less than 2,000 tickets remaining. It will be Japan's first encounter against Wales in Cardiff since 2007.
Wales team to face Japan:
Liam Williams (Scarlets); L Halfpenny (Toulon), J Davies (Scarlets), J Roberts (Harlequins), A Cuthbert (Cardiff Blues); G Anscombe (Cardiff Blues), Lloyd Williams (Cardiff Blues); N Smith (Ospreys), S Baldwin (Ospreys), S Lee (Scarlets), C Hill (Newport Gwent Dragons), A W Jones (Ospreys), D Lydiate (Ospreys), S Warburton (Cardiff Blues, capt), J King (Ospreys).
Replacements: K Dacey (Cardiff Blues), R Gill (Cardiff Blues), S Andrews (Cardiff Blues), J Ball (Scarlets), R Moriarty (Gloucester), G Davies (Scarlets), S Davies (Ospreys), K Giles (Ospreys).