Twice a losing finalist in 2015 and 2016 - each time to Chile - the Albiceleste came third at the tournament two years ago after losing in the semi-finals to Brazil.
While they did at least defeat La Roja in that bronze-medal match, those two penalty shoot-out losses were tough to swallow for Messi, who has been unable to match his remarkable club success for his country.
Only Uruguay (15) have won this tournament more often than Argentina (14), but their last title came in 1993 and they have lost four consecutive finals, having also been beaten in 2004 and 2007.
Argentina hold the records for both most goals scored (462) and most appearances (195) in the history of the Copa America and can at least feel buoyed by the fact they have not lost a match since that 2-0 defeat to Brazil in the last four in 2019.
They drew with Chile and Colombia in their most recent matches in World Cup qualifying, each time after taking the lead, but there appears to be a growing belief within the squad around coach Lionel Scaloni's ideas.
"The truth is the team is really well, the group is really well. We're getting to know each other more and consolidating the coaching staff's idea," Giovani Lo Celso said this week, as per Ole.
"As we know, all South American teams and matches are very difficult. It's all very balanced, very competitive and we know there are no easy games. It's going to be a very difficult group."
Chile's preparations were blighted by a foot injury suffered by Alexis Sanchez, with the Inter forward not now expected to be fit until the knockout phase.
They have only won three matches since the previous tournament and have only played three games this year under coach Martin Lasarte, who took charge in February.
PLAYERS TO WATCH
Argentina – Lionel Messi
Still the go-to star for Argentina 16 years after his debut, this year's Copa America and the 2022 World Cup look like being Messi's final chances for international glory.
He might be turning 34 this month, but his powers remain imperious: he was directly involved in 50 goals (38 scored, 12 assisted) in 47 games for Barcelona in 2020-21. Only three players in Europe's top-five leagues managed more.
Chile – Carlos Palacios
An unknown at senior tournament level, Carlos Palacios will be familiar to some crowds in Brazil, having joined Internacional on loan from Union Espanola this year.
Still awaiting a first start for his country, the 20-year-old could well be called upon in the absence of Sanchez as Chile bid to come through Group B games with Argentina, Bolivia, Uruguay and Paraguay.
KEY OPTA FACTS
- Argentina are unbeaten in their 28 Copa America clashes with Chile. Their 28 games are the most against a single opponent without defeat in their Copa America history.
- Chile's two Copa America titles came in consecutive editions – claiming glory in both the 2015 and 2016 tournaments.
- Argentina have beaten every single opponent in this year's Copa America more times than they have lost to them in tournament history.
- Chile made it at least to the quarter-finals in seven of the past eight editions.