Uruguay won the first Copa America in 1916 and kept their momentum going through to the first World Cup, which they lifted in 1930.
With that inaugural Copa success coming on Argentinian soil, the home side will not be taking Forlan and company lightly on Saturday at Santa Fe.
Historians of the world's oldest surviving international tournament also will point out that for the first six of Uruguay's 14 continental successes they beat Argentina, who also have 14 crowns, in the final.
It took until 1927 before the boot was on the other foot.
The Argentinians have won six Copas in eight hostings of the event - but on the other two occasions it was the Uruguayans who proved too strong, including in 1987, when even Diego Maradona could not prevent defeat as the then world champions finished fourth.
Argentina have famously won nothing at senior level since the 1993 Copa while Uruguay won the 1995 event and then trailed off until they reached last summer's World Cup semi-finals.
The pair's head-to-head record reads 13-13 but both are looking to their star men, Messi for the hosts, and Forlan for the Uruguayans, to turn the tide their way this time.
"This match will generate interest around the world," predicted Uruguay striker Sebastian Abreu.
"Both countries have 14 titles and the winner will be well on the way to winning a 15th."
Veteran Abreu says the task is to shackle Messi, although he admits he loves watching the Barcelona man play.
"You have to enjoy watching Messi - we're going up against the best player in the world. But Colombia kept him under wraps with a compact team.
"What we have to do is make sure we create a few chances," said Abreu of Brazilian side Botofogo.
Uruguay coach Oscar Tabarez also believes Messi could be key.
"Messi can create a lot of problems for us that are not going to disappear," he said.
"But, happily, we can also do a lot of things that neither Messi nor anybody else can prevent."
Argentina coach Sergio Batista, who hopes Messi will show his club form, as he did against Costa Rica, may opt to take Gonzalo Higuain out of the starting line-up on Saturday.
Batista is believed to be pondering adding Esteban Cambiasso or else Lucas Biglia and taking out Real Madrid striker Higuain, who missed several chances against Costa Rica, in what would be a slightly more cautious line-up than the one which flattened the less wily Ticos.
Uruguay coach Oscar Tabarez meanwhile promises that "it will be do-or-die and now the tournament is really beginning in earnest".
The last time sky blue and white went up against sky blue at the Copa was at the 2004 edition in Peru, when Argentina won an opening-round meeting 4-2.
Argentina went on to lose the final on penalties to Brazil, who thumped them 3-0 in the last final in 2007. Hence, the hosts' burning desire to stop the auriverde - meeting Paraguay on Sunday - from completing a hattrick.