The two-time World Cup winners are without their most famous player and leading goalscorer of all time, but there is still plenty of talent within the squad.
They may be defending champions and the record winners of the Copa America, yet a lot of the focus heading into the 44th edition of the competition has centred around the man that will be not be in Chile - Luis Suarez.
The Barcelona frontman, who recently helped his side to win a La Liga, Copa del Rey and Champions League treble, was voted the Player of the Tournament in 2011 in recognition of his four-goal haul. However, his infamous bite of Italy centre-back Giorgio Chiellini last summer means that while he is permitted to play club football, he is still banned from representing his country.
In his absence, plus the omission of the retired Diego Forlan, the goalscoring burden will rest on the shoulders of Edinson Cavani, a scorer of 31 goals in all competitions for Paris Saint-Germain last term. His record at international level is also impressive, having scored 27 goals from his 72 caps.
The Uruguayans will be hoping that Cavani's goals fire them to a 16th Copa America, having won it for a record 15th occasion in Argentina four years ago.
Oscar Tabarez's men can take confidence from the fact that since the Argentines lifted the trophy in 1991, there have been three successful defences, although Uruguay failed to do so in 1995.
With top spot and possibly an easier quarter-final for the winner of Group B, it is vitally important that the Uruguayans lay down a marker against the Jamaicans, particularly with games against Argentina and the potentially tricky Paraguay to come.
Recent form: DDWDWW
Recent form (all competitions): DWDWWW
This will be the first time that the competition has featured the Jamaicans, who accepted an invitation to feature from the South American Football Confederation.
While they have no previous Copa America history, their international tournament record is a mixed bag.
'The Reggae Boyz' are fondly remembered for the carefree way in which they played their football at France '98, where they recorded a famous win over Japan, but they have failed to qualify for any of the four World Cups since then. On the flip side, they have won four of the last nine Caribbean Cups.
In former Borussia Monchengladbach player Winfried Schafer, Jamaica have a head coach with previous international experience. During his three years at the helm of Cameroon, the 65-year-old guided the Indomitable Lions to success at the 2002 Africa Cup of Nations, as well as a runners-up spot at the following year's Confederations Cup.
However, up against such established nations in Chile, the German boss may find that he has his work cut out. The last time that Jamaica faced a big-name international side was back in June 2014, in a game that saw France romp away as 8-0 winners.
As far as the bookmakers are concerned, they are the rank outsides to go all the way in the tournament, with some offering odds of 500-1.
Recent form: DWWDWW
It has already been mentioned that Cavani will lead the Uruguay attack, but there is a question as to whether he will have a partner or play as lone frontman.
Youngster Diego Rolan featured alongside Cavani during a recent friendly against Guatemala, and there have been suggestions that he will keep his place as reward for his goalscoring contribution.
Elsewhere, Atletico Madrid duo Diego Godin and Jose Gimenez should continue their partnership in the centre of defence, with their club teammate Cristian Rodriguez also pushing for inclusion in midfield.
As for Jamaica, there are likely to be a host of familiar faces in their starting lineup for fans of English football.
Uruguay possible starting lineup:
Muslera; M Pereira, Godin, Gimenez, A Pereira; Rodriguez, Lodeiro, Arevelo, Sanchez; Cavani, Rolan
Jamaica possible starting lineup:
Miller; Taylor, Morgan, Mariappa, Lawrence; Watson, Barnes, Austin, McAnuff; Mattocks, Brown
Head To Head
Despite this game marking Jamaica's Copa America debut, this will be the fourth occasion they have faced Uruguay.
The first came in 1974, with the South Americans running out 3-0 winners, before they then recorded a 2-0 victory in the year 2000.
We say: Uruguay 3-0 Jamaica
With big games to come, Uruguay will be looking to make a statement in this encounter. They will play on the front foot and look to dominate possession. Assuming that they take some of the numerous chances that they are expected to create, it should be a comfortable margin of victory.