Up to six teams were in contention to claim fifth spot and book a meeting with Oceania confederation champions New Zealand heading into the matches and Peru were set to miss out altogether as they trailed 1-0 at home to Colombia in Lima.
Legends of the game such as Ryan Giggs, Alfredo Di Stefano, George Best, Eric Cantona and Ian Rush are just a number of players who never even made it to a World Cup.
Argentina went into the clash needing a win to book a place at the finals in Russian Federation - and Messi cancelled out Romario Ibarra's opener with an 11th minute strike.
The top four teams in the South American zone group will earn an automatic ticket to Russian Federation while the fifth-ranked side will book a playoff spot.
Martin Caceres and Edinson Cavani scored twice just before half-time to give Uruguay the lead before two goals from Luis Suarez put the hosts 4-1 up.
Messi, who will turn 31 during next year's World Cup, now has one, perhaps final, chance to emulate his idol Diego Maradona by lifting the World Cup.
This would mean no Lionel Messi to drive television ratings; no Messi to spur ticket sales for local organizers; no Messi to distract from off-field controversies surrounding the world-governing body, FIFA.
It would be embarrassing for Argentina if they become one of the biggest absentees of World Cup 2018.
Finally we reach Lionel Messi and Argentina, now in sixth place in the CONMEBOL standings. "This is what we came for".
While Messi scored his first ever hat-trick goals in 2007 for FC Barcelona, his first worldwide Hatrick came against Switzerland in a friendly match. His second spectacular hat-trick performance was also witnessed in 2012 in the Argentina vs Brazil match played on June 9, 2012.
Had Ospina not touched it the goal would have been disallowed and Chile would have replaced Peru in the play-offs despite their own 3-0 defeat to Brazil.
Nigeria became the first African country to progress when Arsenal's Alex Iwobi scored the victor against Zambia on Saturday, while a stoppage-time penalty from Liverpool's Mohamed Salah the following day took Egypt to their first World Cup in 28 ye ars. The Argentine was successful as Chile's coach, and at Spanish club Sevilla.
In that doomsday scenario, it would depend on the result of the Peru-Colombia result as to whether Chile finished fifth or sixth.