Clifford in novice England back row
Clifford, fit following a chest injury, has been called into the starting side by coach Eddie Jones while Wood, who has been struggling with a chest injury, is demoted to the bench.
The only other change to the England starting XV that beat France 19-16 at Twickenham in the Grand Slam champions tournament opener is on the wing, with Jack Nowell replacing Jonny May after the latter was sin-binned against the French.
May, like Wood, is now on the bench.
England could find themselves up against a vastly experienced Welsh loose forward trio comprising three British and Irish Lions, but Clifford, Maro Itoje – best known as a lock – and Nathan Hughes have just four back-row starts between them, while Wood has 46 caps.
"Jack Clifford also deserves his starting role. He is a hard-working, young player," Jones said in a Rugby Football Union statement.
"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," the Australian added.
"Tom Wood will also play his part later in the game off the bench as a finisher."
England are on a national record 15-match winning streak, just three short of equalling world champions New Zealand's all-time tier one record of 18 successive Test victories.
England: 15 Mike Brown, 14 Jack Nowell, 13 Jonathan Joseph, 12 Owen Farrell, 11 Elliot Daly, 10 George Ford, 9 Ben Youngs, 8 Nathan Hughes, 7 Jack Clifford, 6 Maro Itoje, 5 Courtney Lawes, 4 Joe Launchbury, 3 Dan Cole, 2 Dylan Hartley (captain), 1 Joe Marler.
Replacements: 16 Jamie George, 17 Matt Mullan, 18 Kyle Sinckler, 19 Tom Wood, 20 James Haskell, 21 Danny Care, 22 Ben Te'o, 23 Jonny May.
Date: Saturday, February 11
Venue: Millenium Stadium, Cardiff
Kick-off: 16.50 (16.50 GMT)
Referee: Jérôme Garcès (France)
Assistant referees: Pascal Gauzère (France), Nick Briant (New Zealand)
TMO: Glenn Newman (New Zealand)
Agence France-Presse
