Both nations have aspirations to finish at the top of their Euro 2024 qualification group, which also features Turkey, Armenia and Latvia.
Match preview
There has been a feeling that Wales have been closing in on an end to an era for some time, and that was rubber-stamped when Bale hung up his boots after the World Cup.
In the short term, that is a considerable blow to this team, yet it will only encourage a greater togetherness now that they cannot rely on the individual brilliance of their greatest-ever player.
On the back of eight matches without success and a dismal World Cup campaign, that will be required if they are not to drop down the international pecking order.
While this group is more favourable than it could have been, there will be an acknowledgement that Robert Page's side are in a fight to finish in second spot behind their upcoming hosts.
That particularly rings true with Wales having never recorded a win over Croatia, losing three successive times on away territory since a 1-1 draw in 2002.
Croatia also faced the prospect of eras coming to an end after a third-placed finish in Qatar, yet the likes of Luka Modric and Ivan Perisic have remained active on the international scene when Dejan Lovren has announced his national team retirement.
Zlatko Dalic will be delighted with the pair offering invaluable experience to the rest of the squad as they make another assault at trying to get over the line at a major tournament.
The Checkered Ones head into this qualifying campaign having lost just one of their last 13 matches in all competitions, that defeat being to eventual world champions Argentina at the semi-final stage.
Since the start of 2021, Croatia have succumbed on just one occasion in home fixtures, highlighting the size of Wales' task as they square off against the second-best performing European side in Qatar.
Croatia form (all competitions):
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D
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Wales form (all competitions):
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L
Team News
With Lovren having brought an end to his international career, Josip Sutalo could get the nod in the centre of defence alongside Josko Gvardiol.
Nikola Vlasic is one of a number of alternatives to Mario Pasalic on the right flank, but much of the Croatia team which began the World Cup semi-final versus Argentina could start this match.
Wayne Hennessey and Ben Davies have both been forced to withdraw from the Wales squad, with Danny Ward and Ben Cabango in line to feature ahead of the pair.
The middle five should be as expected, with Ethan Ampadu being preferred there to defence and Aaron Ramsey captaining the side.
Brennan Johnson may get the nod over Daniel James to partner Kieffer Moore in attack.
Croatia possible starting lineup:
Livakovic; Juranovic, Sutalo, Gvardiol, Sosa; Modric, Brozovic, Kovacic; Vlasic, Kramaric, Perisic
Wales possible starting lineup:
Ward; Mepham, Rodon, Cabango; Roberts, Ramsey, Ampadu, Wilson, Williams; Johnson, Moore
We say: Croatia 2-0 Wales
Although Wales have other quality players that they can call upon, none of them can match the quality that was offered by Bale. Against quality opposition, they may come up short, leading us to predict a relatively comfortable triumph for the home side.