England coach Jones (left) has brought in Clifford (centre) and Nowell for the Wales game
Flanker Tom Wood has been dropped to the bench despite being given the all clear to face Wales in Cardiff.
Wood sustained a shoulder injury in the 19-16 win over France last week.
And Nowell comes in on the wing for Jonny May, who is also sent to an otherwise unchanged bench.
“Jack Nowell starts this week with Jonny May changing to a finisher," said Jones.
England Rugby's 14-game winning streak
Fri, January 6, 2017
Express Sport recaps England Rugby's unbeaten 2016
1 of 15
England won every single match they played throughout 2016, and are currently on a 14-game winning run dating back to October 2015
"Jack has an excellent work-rate and he’s a guy that carries through the line which will be important for us.
“Jack Clifford also deserves his starting role. He is a hard-working, young player.
"He has got a good record against Wales, he had a superb game against them in May, he knows what he is going to expect from Wales and we’re looking forward to him making an impact to our back-row play.
"Tom Wood will also play his part later in the game off the bench as a finisher."
Jack Clifford (centre) comes into the England pack
Tom Wood suffered an injury in the game against France
England laboured to a victory over the French at Twickenham last weekend to stretch Jones' winning run with the side to 15 games.
They travel to Wales seeking to maintain their bid for a second successive Grand Slam.
But Jones has warned his men will not be complacent as Wales, who beat Italy 33-7 last week to earn a bonus point, also seek Six Nations glory.
“We don’t need extra motivation this week; we play Test rugby because we want to be the best for England," he added.
"Every game for us is important and our supporters, and Wales is our next game so it’s the most important.”
England XV to face Wales
15. Mike Brown (vice captain, Harlequins, 56 caps)
14. Jack Nowell (Exeter Chiefs, 19 caps)
13. Jonathan Joseph (Bath Rugby, 30 caps)
12. Owen Farrell (vice captain, Saracens, 48 caps)
11. Elliot Daly (Wasps, 9 caps)
10. George Ford (Bath Rugby, 31 caps)
9. Ben Youngs (Leicester Tigers, 66 caps)
1. Joe Marler (Harlequins, 47 caps)
2. Dylan Hartley (captain, Northampton Saints, 80 caps)
3. Dan Cole (Leicester Tigers, 70 caps)
4. Joe Launchbury (Wasps, 38 caps)
5. Courtney Lawes (Northampton Saints, 54 caps)
6. Maro Itoje (Saracens, 8 caps)
7. Jack Clifford (Harlequins, 8 caps)
8. Nathan Hughes (Wasps, 4 caps)
16. Jamie George (Saracens, 13 caps)
17. Matt Mullan (Wasps, 14 caps)
18. Kyle Sinckler (Harlequins, 4 caps)
19. Tom Wood (Northampton Saints, 46 caps)
20. James Haskell (Wasps, 71 caps)
21. Danny Care (Harlequins, 67 caps)
22. Ben Te’o (Worcester Warriors, 4 caps)
23. Jonny May (Gloucester Rugby, 23 caps)