Bale, Sanchez, Pulisic and Vidal - the all-star XI missing Russia 2018
European champions Portugal were left playing catch-up after losing to Switzerland in September last year but overcame the same opponents 2-0 in Lisbon to pip them on goal difference.
Argentina were staring elimination in the face when Ecuador took an early 1-0 lead in Quito before a virtuoso showing by Messi ended with the talisman completing a mesmerising hat-trick.
However, other stars of the world game have not been so fortunate and there will be more high-profile casualties to come during next month's play-off clashes.
For now, here is a mightily impressive "dream team" whose efforts to reach the World Cup turned into nightmare.
GOALKEEPER – Jan Oblak (Slovenia)
Atletico Madrid number one Oblak is one of the finest goalkeepers on the planet and conceded only seven times during 10 qualifiers for Slovenia. Unfortunately, they could only manage 12 at the other end as they limped to fourth place in their group behind England, Slovakia and Scotland.
Jan Oblak je med kandidati za prestizno nagrado Zlata zoga! #BallonDor #SrceBije pic.twitter.com/1gGmgWK1rm
— NZS | FA Slovenia (@nzs_si) October 9, 2017
RIGHT-BACK – Antonio Valencia (Ecuador)
Suspension spared Manchester United full-back Valencia from having to counter a Messi masterclass but nine defeats from the previous 17 CONMEBOL preliminary matches meant Ecuador were only ever playing for pride in the face of greatness.
Mientras tú duermes, Yo trabajo!While you sleep, I work! pic.twitter.com/xmhNCKJhCt
— Antonio Valencia (@anto_v25) October 3, 2017
LEFT-BACK – David Alaba (Austria)
The disappointment of a sapping group-stage exit at Euro 2016 spilled into the World Cup campaign for star man Alaba and Austria, who stumbled to fourth place in European Group D behind Serbia, Republic of Ireland and Wales.
CENTRE-BACK – Gary Medel (Chile)
Cap centurion and long-serving hard man Medel was unable to stem the tide as Chile lost three of their last four qualifiers, shipping eight goals in the process to finish the gruelling CONMEBOL slog in sixth. Fifth-placed Peru pipped them to a play-off place, seemingly closing a golden era for the two-time reigning South American champions.
Mañana todos juntos chilenos #guerreros #lafeintacta #vamoschilectm pic.twitter.com/9CBVGmFf1Y
— Gary Medel (@MedelPitbull) October 10, 2017
CENTRE-BACK – Virgil van Dijk (Netherlands)
Beaten finalists in 2010 and 2014 semi-finalists, Netherlands have now missed out on a second consecutive major tournament. As star winger Arjen Robben moves into international retirement, Southampton centre-back Van Dijk is among a talented core who will aim to repair considerable damage.
MIDFIELD – Miralem Pjanic (Bosnia-Herzegovina)
Juventus playmaker Pjanic will not bring his silken qualities to Russia after a shock loss to Cyprus in August proved pivotal in terms of Greece sealing the Group H play-off spot at Bosnia-Herzegovina's expense behind runaway winners Belgium.
MIDFIELD – Arturo Vidal (Chile)
The beating heart of Chile's recent successes, combustible Bayern Munich hero Vidal has strongly hinted he will walk away from international football on the back of Tuesday's decisive 3-0 defeat against Brazil in Sao Paulo.
Gracias por todo muchachos!! pic.twitter.com/I9s9OhTK7r
— Arturo Vidal (@kingarturo23) October 11, 2017
MIDFIELD – Christian Pulisic (United States)
Borussia Dortmund sensation Christian Pulisic is one of the brightest teenage talents in the world. His chance to shine on the biggest stage should come around a few more times. First there will be a lengthy inquest into the USA's embarrassing CONCACAF implosion.
Workin' them angles.@cpulisic_10 takes Panama to school. pic.twitter.com/clhz0Zynk1
— U.S. Soccer (@ussoccer) October 7, 2017
FORWARD – Alexis Sanchez (Chile)
A national hero for his exploits with La Roja, Sanchez bemoaned criticism levelled at himself and his team-mates as Chile's campaign fell apart. The impact of his transfer saga with Manchester City occurring around the crushing 3-0 defeat to Paraguay may well be debated for some time.
FORWARD – Pierre-Emerick Aubameyang (Gabon)
Everything Aubameyang touches with Borussia Dortmund tends to turn to gold but he was unable to lift his countrymen to a maiden World Cup. Gabon will be a footnote in Africa's Group C as heavyweights Morocco and Ivory Coast contest a winner-takes-all clash.
FORWARD – Gareth Bale (Wales)
Bale has been the poster boy of a golden generation for Welsh football, starring on the run to the Euro 2016 semi-finals. It was particularly cruel, therefore, to see injury restrict him to a seat in the stands in Cardiff as the Republic of Ireland ensured Wales' wait for a second World Cup finals berth will tick past 60 years.
Hard loss to take last night, but couldn’t be more proud of the team, we leave with our heads held high #TogetherStronger pic.twitter.com/8jyy227eXO
— Gareth Bale (@GarethBale11) October 10, 2017