But the hosts quickly found their boast, and a second-half effort by Conor Coady with a superb bike kick from Danny Ings earned the Three Lions a routine victory.
Wales are now focused on their huge Nations League fixtures with Republic of Ireland and Bulgaria, with Ryan Giggs’ side looking to maintain their 100% winning start in the competition.
Giggs was without Gareth Bale, Aaron Ramsey and Joe Allen as a trio for only the second time in his tenure as boss so far, with the 1-0 triumph over Trinidad and Tobago in March 2019 being the only other occasion the three these stars were not available.
Wayne Hennessey was on par with legendary goalkeeper Neville Southall with 92 caps for Wales, while Chris Mepham and Joe Rodon both returned to center-back after missing the previous camp with injury , Ethan Ampadu passing to midfield as a result.
In the absence of Bale and Ashley Williams, Tottenham star Ben Davies led visitors to the English capital as Rabbi Matondo received his first departure for his country as part of three offensives which included Tyler Roberts and Kieffer Moore.
Southgate also made plenty of changes, with Nick Pope replacing Jordan Pickford in the goal while Kieran Trippier wore the armband while Harry Kane was rested.
Calvert-Lewin and Bukayo Saka made their debuts in what was a very inexperienced starting line-up in England.
Giggs’ side came into the game after winning their last four games without conceding a single goal while being unbeaten in their previous eight outings.
However, despite being devoid of stars such as Jadon Sancho, Raheem Sterling and Kane, the Three Lions – who entered the game without losing to Wales since 1984 – have remained bookmakers’ favorites to come out. victorious.
In preparation for the match, Giggs and his players were very convinced that the game was a friend, with the boss admitting that the Nations League was his priority.
The lack of 90,000 supporters did little to dampen player enthusiasm, and they wore black armbands in tribute to those who lost their lives to the coronavirus during the pandemic, as well as former international Keith Pontin and fan Mike Dye who died outside Wembley during Wales’ last visit to Wembley in 2011.
Wales seemed comfortable in possession from the start, and Moore once again provided his side with a focal point while Matondo caused some issues with his pace.
It was the hosts who carried the greatest threat, however, with Ings charging a clearance from Hennessey before the tame Calvert-Lewin shot was cleared by Mepham after the Everton man bypassed the Country goalkeeper. Wales.
The outside side was set to advance midway through the first half as the ball fell nicely on Moore inside the box, although the Cardiff man flew right past Pope’s goal .
But just as the hosts seemed lacking in creativity, the impressive Jack Grealish found a space on the right before choosing Calvert-Lewin, who drove at home his 10th goal of the campaign for club and country.
It was a cruel blow to Wales who to their credit responded well, and Pope had to be vigilant to refuse Mepham from a corner before closing Moore who was unable to pull the trigger after controlling to expertly a long ball forward.
Moore then needed treatment after taking a hit as the Three Lions gained confidence, with Coady shooting from inside the box just before the break.
Neco Williams then replaced Moore, who was unable to continue as the visitors entered the break one goal behind.
Wales had not won a match after conceding the first since their famous Euro 2016 quarter-final triumph over Belgium.
And Tyler Roberts – who led the line in Moore’s absence – pulled a wide shot shortly after the restart as Wales looked to respond after Ben Cabango and Dylan Levitt replaced Rodon and Joe Morrell respectively.
But Wales’ defensive neglect was once again costly in the 53rd minute, as Coady stole Trippier’s free kick to double England’s lead.
Matondo hit the inside of the post from an offside position before Southgate made a triple substitution with Mason Mount, Tyrone Mings and Reece James all called up.
And it went from bad to worse for Wales just past the hour mark, as Ings found himself in acres of space in the box before shooting a spectacular kick past Hennessey.
Saka almost made four, although his deflected strike was superbly saved by Hennessey.
Chris Gunter and Matt Smith replaced Connor Roberts and Jonny Williams late respectively after substitute Will Vaulks shot well over with Hennessey making another stunning save, this time to deny Ings.
And Wales were unable to register what would have been only a consolation strike as they lost for the first time since being beaten by Hungary in June 2019.
England: Le pape; Gomez (Mings 58), Coady, Keane; Trippier (C) (James 58), Phillips, Winks (Ward-Prowse 75), Saka (Maitland-Niles 75); Grealish (Barnes 75); Ings, Calvert-Lewin (mont 58).
Unused Submarines: Henderson, Pickford, Rashford, Alexander-Arnold, Maguire, Rice.
Buts: Calvert-Lewin 26, Coady 53, Ings 63
Wales: Hennessey; C Roberts (Gunter 73), Mepham, Rodon (Cabango 46), B Davies (C); Morrell (Levitt 46), Ampadu (Vaulks 62), J Williams (Smith 73); T Roberts, Moore (N Williams 39), Matondo.
Unused Submarines: Ward, A Davies, Johnson, Norrington-Davies, James, Woodburn.
Yellow cards: C Roberts 42, Ampadu 58, Levitt 62
Arbitre: Bobby Madden
How the match went: