This fixture will complete the first round of fixtures in Group B, an intriguing section involving England and Iran which could be very tight.
Match preview
The US are back at the World Cup finals after missing the 2018 edition in dismal fashion following a defeat in Trinidad & Tobago in their final qualifier.
This time around, it was still a close run affair in a very difficult qualifying section where the top four nations were separated by just three points, but the USA managed to claim one of the three automatic spots, just ahead of Costa Rica.
Gregg Berhalter has raised a few eyebrows with his squad selection, leaving out a few players who have been regulars in the squad over the past few years, but after form had tailed off slightly in preparation for the finals, change was likely.
Following qualification, USA beat Morocco and Grenada while earning a draw against Uruguay, but a draw in El Salvador, only managed after an injury-time equaliser in the CONCACAF Nations League, plus defeat to Japan and a draw with Saudi Arabia in September friendlies brought some discontent.
The United States have reached the knockout round in four of their last seven tournament appearances, but they have failed to beat European opposition in their previous nine attempts, so if they want to progress this time, they will surely need to end that run with two UEFA nations in their group.
Wales's form coming into the finals does not offer much optimism either, as they have not won since sealing their place in Qatar with that 1-0 success over Ukraine in the playoffs.
A 1-1 draw with Belgium was the only point Rob Page's side managed in their recent Nations League campaign, as home and away defeats to Poland and the Netherlands saw them relegated from League A.
That was in major contrast to their form in qualifying for this World Cup, where despite losing their opener fixture with Belgium, Wales remained unbeaten in the following seven matches in the group to finish above the Czech Republic.
All eyes will be on Gareth Bale once again, as the former Real Madrid star will be the leading light for the Welsh following his heroics in the playoffs - scoring twice against Austria in the semi-final, and claiming the assist for Andriy Yarmolenko's own goal in the final.
Wales made it through the group stage at their two recent major tournament appearances at Euro 2016 and 2020, and Bale will want to ensure they do so again, considering this could be his swansong in the colours of his nation.
USA form (all competitions):
W
D
W
D
L
D
Wales form (all competitions):
W
L
D
L
L
L
Team News
Zack Steffen was expected to wear the gloves for the United States in Qatar, but an uninspiring season with Manchester City, which saw him replaced by Stefan Ortega as backup, has led to him losing his place in the squad altogether.
Matt Turner and Ethan Horvath are the two men set to battle it out to start in goal, and Arsenal man Turner played in both September friendlies so may have the upper hand.
Weston McKennie has not featured for Juventus since October, but should be fit in time to feature from the start in midfield here.
The main strength for the US comes in the attacking third, with many options available to Berhalter, meaning one or two may be unfortunate to miss out, as Timothy Weah, Gio Reyna and Jesus Ferreira are all staking a claim to start in attack alongside Christian Pulisic.
Gareth Bale revealed earlier in the week that he is ready and prepared to play 90 minutes in all three of Wales's group games if necessary, despite him being reduced to mainly cameo appearances since joining LAFC in MLS this year.
Joe Allen has been out injured since late September, but he believes he'll be ready to take part in this group opener.
However, defender Rhys Norrington-Davies has not been as fortunate, as the Sheffield United man will not play any part in the tournament for Wales, following his injury against Coventry City last month.
USA possible starting lineup:
Turner; Dest, Zimmerman, Long, A Robinson; Adams, McKennie, Aaronson; Reyna, Ferreira, Pulisic
Wales possible starting lineup:
Hennessey; C Roberts, Ampadu, Rodon, B Davies, N Williams; Allen, Ramsey; Bale, Moore, James
We say: USA 1-1 Wales
With England favourites to win the group, the fight for second place in the group could be extremely close, and neither side can afford to lose this crunch opener.