Captain Sam Warburton, 91 times-capped prop Gethin Jenkins and fly-half Rhys Priestland are among those on bench duty after starting last Saturday's clash against Argentina that ended in a deflating 26-12 defeat.
Ryan Jones takes over as skipper for a Wales record 29th time - eclipsing the mark he previously held alongside Ieuan Evans - while considerable interest will surround starting fly-half Dan Biggar and openside flanker Justin Tipuric, who replaces Warburton.
"With a short six-day turnaround it was important for us to freshen things up and also make use of the competition for places we have within this squad," Wales' interim head coach Howley said.
"It is something which has been a key ingredient for the success of the squad over the last 18 months.
"In making changes, we also needed to bring in some genuine experience.
"It is important to have leaders throughout the team, and we are hoping the likes of Mike Phillips, who made a positive impact last week (off the bench), can bring his experience to the side.
"Ryan reaches an impressive personal milestone. It will be a huge honour for him, but in the context of what happened last week his and the team's priorities are about producing a performance.
"We know we are under pressure to perform, and that pressure is greatest from within."
Blindside flanker and skipper Jones replaces knee ligament victim Josh Turnbull, with lock Bradley Davies taking over from Alun-Wyn Jones (shoulder) and hooker Richard Hibbard in for Matthew Rees (calf muscle).
Elsewhere, there are starts for scrum-half Phillips, centre Ashley Beck and prop Paul James as Wales target a first victory since they beat the Barbarians more than five months ago.
Jones, who will win his 68th cap, knows the pressure is on his team to deliver against a Samoa side that ran Wales perilously close in World Cup combat last year before succumbing 17-10.
"We need to get back into winning ways," Jones said.
"We need to put a few things right tactically and technically, and we need to get a good result under our belt.
"There is a feeling and a real desire to put it right this week, which is what we need.
"The process is the same. You look at it - win or lose - you analyse it and pick the bones out of it, but you have got to move on."
The Samoa line-up includes seven players based with British clubs, including Northampton centre George Pisi, Worcester wing David Lemi, Ospreys scrum-half Kahn Fotuali'i and Harlequins flanker Maurie M Fa'asavalu.
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