In the battle of the two remaining unbeaten sides in this year’s Championship, Nowell – who appeared in both the second and third Tests on the Lions 2017 Tour to New Zealand – comes back onto the right wing.
Another Test Lion Mako Vunipola is ruled out with injury however, so Ben Moon gets the nod to start at loosehead prop in the only other change to the starting XV from the England side that downed France in Round Two.
Brad Shields, who played against the Lions on that 2017 Tour for the Hurricanes, comes onto the bench this weekend and could make his Red Rose Championship debut if called upon in the Cardiff cauldron.
England head coach Eddie Jones said: “Ben Moon will start and Ellis Genge will finish so we will get a great 80 minutes out of those two.
“It is disappointing to lose a player of the calibre of Mako Vunipola but we have two very good players who will do a great job for us.
“Jack Nowell will start and Joe Cokanasiga will come onto the bench. As we saw in the autumn Joe is a player of great potential so we are looking forward to him adding to the squad.
“Brad Shields comes in for Nathan Hughes as a finisher as we just feel like it is going to be a high work-rate game.”
Wales are on a record-equalling Test run of 11 consecutive wins while England are top of the standings after two bonus-point wins from two.
England have won the last five Championship meetings between the two sides however, and Jones cannot wait to sample what Principality Stadium has to offer.
He added: “England and Wales is always a big game. Intense rivals and there is the historical context to it, but for us it is our most important game because it is our next game and that is how we are treating it.
BREAKING | Your England team to face Wales on Saturday in the #GuinnessSixNations
Preview ➡ https://t.co/HbpHbeEotO#WALvENG #CarryThemHome 🌹 pic.twitter.com/XrtjKeJkie
— England Rugby (@EnglandRugby) February 21, 2019
“Whenever you play against a Warren Gatland side you are playing against a side that is going to be very physical on the gain line. They are always very fit so you have to make sure you win the gain line and then find opportunities of where you are going to attack them.
“As you have read in the media, it’s all about Wales, we are playing potentially the greatest team ever.
“Their players are full of emotion and it’s the biggest game they are going to play in their lives. We have had a good week just focussing on ourselves and focussing on getting our preparation right.”
England starting XV
15 Elliot Daly (Wasps)
14 Jack Nowell (Exeter Chiefs)
13 Henry Slade (Exeter Chiefs)
12 Manu Tuilagi (Leicester Tigers)
11 Jonny May (Leicester Tigers)
10 Owen Farrell (Saracens) (captain)
9 Ben Youngs (Leicester Tigers)
1 Ben Moon (Exeter Chiefs)
2 Jamie George (Saracens)
3 Kyle Sinckler (Harlequins
4 Courtney Lawes (Northampton Saints)
5 George Kruis (Saracens)
6 Mark Wilson (Newcastle Falcons)
7 Tom Curry (Sale Sharks)
8 Billy Vunipola (Saracens)
16 Luke Cowan-Dickie (Exeter Chiefs)
17 Ellis Genge (Leicester Tigers)
18 Harry Williams (Exeter Chiefs)
19 Joe Launchbury (Wasps)
20 Brad Shields (Wasps)
21 Dan Robson (Wasps)
22 George Ford (Leicester Tigers)
23 Joe Cokanasiga (Bath Rugby)