La Roja went all the way in 2010 for their first and only success in the quadrennial competition, while their opponents head into the tournament with their triumphant Euro 2016 campaign still fresh in the memory.
Despite their status as reigning European champions, Portugal are as far down as eighth favourites with some bookmakers to turn that continental success into global success.
Not that those odds will present any sort of problem - the Selecao were similarly placed ahead of Euro 2016, before grinding out result after result to eventually lift the trophy.
That it took Portugal six attempts - against Wales in the semi-finals - to pick up their first victory in normal time mattered little. Fernando Santos made his side incredibly hard to beat in France, and that has remained the case in the two years since.
In fact, under the former Porto, Benfica and Sporting Lisbon boss, Portugal have suffered just two losses in 29 competitive matches, including their penalty-shootout defeat to Chile in last summer's Confederations Cup.
The other loss came in their opening qualifying fixture for the World Cup, going down 2-0 away to Switzerland before winning nine in a row to get themselves over the line. The Swiss deserve credit for pushing Santos's men all the way, and in the end both teams secured a place in the Russia tournament.
Thirty-two goals scored and four conceded in their 10 qualifiers is the type of return you would expect from champions, though the low quality of the Selecao's group - even accounting for sixth-in-the-world Switzerland - has to be factored in.
Portugal's hard-to-beat nature was there to see in their pre-World Cup friendlies, too, although a solitary 3-0 loss to the Netherlands and draws against the United States, Belgium and Tunisia was hardly the best way to build some momentum.
With Cristiano Ronaldo in their ranks, though, and the feel-good factor that comes with winning the Euros, Portugal have a chance to lay down an early marker on Friday against a fellow heavyweight nation.
Recent form: DWLDDW
As far as pre-World Cup controversies go, sacking your manager less than 48 hours before your first match - and a huge match at that - is right up there.
The dismissal of Julen Lopetegui on Wednesday sent shockwaves throughout the football world, as La Roja reacted swiftly to Real Madrid's announcement a day beforehand that the 51-year-old is to become their manager later this summer.
Fernando Hierro, a relatively unknown figure whose only previous managerial experience came in one season at Oviedo, is now tasked with guiding La Roja to a second World Cup triumph in the space of three tournaments.
If that sounds like a daunting task, it has to be remembered that Hierro is taking over one of the most talented groups anywhere on the planet. Some would argue, in fact, that Spain boast the best mix of experience and youth of any side in the competition.
Following a period of domination between 2008 and 2012, winning two Euro crowns and a World Cup in that time, Spain - by their standards, at least - bombed at the next two tournaments.
If their qualifying campaign is anything to go by, however, former boss Lopetegui got them back on track as they dropped just two points, coming in a 1-1 draw with Italy early on.
No team had a better defensive record than the Spaniards, who also netted 36 at the other end, although nearly half of those came in two games against whipping boys Lichtenstein.
Spain were far from their fluid best in warm-up matches against Russia, Germany, Switzerland and Tunisia, but they head into the tournament on a 20-game unbeaten run and, new manager or not, will be heavily backed to match their achievement of eight years ago.
Recent form: WDDWDW
Spain's only fitness doubt ahead of their opening fixture is Dani Carvajal, who limped off in Real Madrid's Champions League final win against Liverpool two-and-a-half weeks ago and has only just returned to training.
Hierro has a decision to make in central midfield, where Andres Iniesta and Sergio Busquets are expected to be joined by one of Thiago Alcantara or Koke, while up top Diego Costa is favourite to get the nod.
Portugal boss Santos also has a selection dilemma of sorts, as Goncalo Guedes and Bruno Fernandes performed well when selected in the 3-0 win against Algeria last week - the Paris Saint-Germain winger scoring twice in Lisbon.
Ronaldo is the undisputed star man in this Selecao side, having netted 81 goals in 150 internationals - 15 of those coming in this most recent qualifying campaign - as well as adding a further 43 strikes to his Madrid tally this term.
Portugal possible starting lineup:
Patricio; Soares, Pepe, Fernandes, Guerreiro; B.Silva, Carvalho, Joao Mario, Martins; Ronaldo, Silva
Spain possible starting lineup:
De Gea; Odriozola, Pique, Ramos, Alba; Alcantara, Busquets, Iniesta; Isco, Costa, Silva
Head To Head
These Iberian neighbours have met on 36 previous occasions, with Spain winning exactly half of those and losing just six.
La Roja have not exactly had things all their own way in more recent times, though, as Portugal have won five and drawn seven of the last 16 encounters since 1950.
The teams last faced off in the semi-finals of Euro 2012 - Spain winning that one on penalties following a stalemate in normal time at the Donbass Arena in Donetsk.
We say: Portugal 1-1 Spain
Portugal tend to start slow in major finals, as they have not got off the mark with three points since Euro 2008. Spain should perform better than four years ago when barely putting up a fight in their title defence, meanwhile, but they have been rocked by the loss of their manager and may take time to settle down. A draw seems an obvious choice, and a result that neither side would be too disappointed with ahead of matches against Morocco and Iran.