Brazil will be under pressure to erase memories of the 2014 World Cup by winning this year's Copa America on home soil, while Lionel Messi and Argentina have a score of their own to settle following disappointment in Russia 12 months ago.
On one of Brazilian football's darkest days, the Selecao were humiliatingly crushed 7-1 by Germany as hosts in the 2014 World Cup semi-finals and they fell a stage earlier in Russia last year.
Argentina were even more underwhelming at the 2018 World Cup than their rivals, finding themselves eliminated in the last 16, with their performances resulting in a major overhaul of the coaching staff and squad.
An ageing Chile will do well to win a third successive title, but both of the favourites have plenty of baggage heading into the tournament.
Can Messi end Argentina's long wait?
Messi's lack of success on the international stage is well-documented and routinely used as a stick to beat him with in the never-ending "greatest player of all time" debate.
"I want to end my career having won something with the national team, or at least try to do so as many times as possible," Messi said to Fox Sports in a recent interview.
He cannot be accused of not trying, having helped his country to four major finals. The past two were in the most recent Copa America editions, losing on penalties to Chile both times.
Argentina have not won a Copa America since 1993, and Messi, 32, is running out of time to be the one who brings them international success again.
Brazil without their poster boy
A big boost to Argentina's chances was the news Brazil talisman Neymar will miss the tournament with an ankle injury, a massive blow for the hosts and favourites.
Nevertheless, such a situation opens the door to others to impress, and in Richarlison, Everton and David Neres, Tite has plenty of options at his disposal.
But Neymar's injury – however crucial in the long run – will not be a valid excuse if Brazil fail again on home soil as they did at the World Cup in 2014.
The pressure is on and the likes of Philippe Coutinho will be expected to carry Brazil to success.
Low expectations for the holders
Back-to-back champions Chile will be under significantly less pressure, however, despite their recent successes in the Copa America.
Coach Reinaldo Rueda has plenty of experience at his disposal, with six centurions in the squad and 11 players who are aged 30 or older.
But there is a startling lack of young talent coming through in Chile presently, with 24-year-old defender Paulo Diaz the youngest outfield player in the selection.
In previous editions such issues might have been ignored given the qualities of Arturo Vidal and Alexis Sanchez, but neither – particularly the latter – are what they once were.
Guest nations out to spoil the party
CONMEBOL has regularly invited guest nations to participate in their showpiece tournament, but for only the second time there will be representatives from countries outside of the Americas playing.
Japan – who also featured in 1999 – and 2022 World Cup hosts Qatar will take their respective places in Group C and Group B, hoping to cause something of an upset.
Qatar won their first Asian Cup title earlier this year and Almoez Ali will be key to their chances of making it out of the group.
Expectations are rather more modest for Japan, however, as coach Hajime Moriyasu has taken a squad mostly made up of players who will be eligible to feature at next year's Olympics.