After taking down another South American giant on Thursday, the hosts will hope to take advantage of what is usually the easiest fixture in CONMEBOL qualifying.
Uruguay achieved the unlikely feat of beating Brazil and Argentina in consecutive qualifiers, after winning away in Buenos Aires last week.
It was a much welcome set of results, after a mixed start had Uruguay lingering around mid-table in the section, with four points from three games.
However, after beating Brazil 2-0 here last month in one of the most cagey matches there will be all season, Marcelo Bielsa took his side away to the world champions and beat them 2-0 on their own turf.
Darwin Nunez has been crucial to their success, scoring in both wins, as well as in an impressive 2-2 draw away at Colombia.
That leaves Uruguay second, just two points off Argentina - who next face Brazil - after ending their 100% start.
Already though, La Celeste look set for a fifth successive World Cup finals appearance, barring any catastrophic slip-ups from this point onwards, recovering well from their group stage exit in Qatar.
Bolivia are the kindest opponents Uruguay could have been given after two hard-fought victories, as their upcoming opponents are among one of the worst away sides in international football.
In their last 66 away World Cup qualifiers, Bolivia have taken just nine points, as it is now over 30 years since their last competitive qualifying win outside of their home country - against Venezuela in 1993.
Qualifying for the 2006 and 2018 World Cups saw Bolivia lose all nine away games, and history could repeat itself after two defeats to start here, and another difficult encounter to come.
A huge win on Thursday at home to Peru should give them some confidence, though, as it lifted them off the bottom following four defeats from four to start.
Despite the expanded format now giving South America a potential for seven nations to qualify, it is unlikely Bolivia will be in the mix, considering they have never won more than four matches out of the 18 that are played, all of which usually come at home.
Boris Cespedes was initially a surprise omission from the Bolivian squad, but he was not missed as they ran out 2-0 winners against Peru on Thursday.
After keeping a clean sheet, Jose Sagredo is set to start again at centre-back in what would be his 50th cap.
Henry Vaca was among the goalscorers in that win, despite it being his first appearance since the last round of qualifiers, as his Israeli club side Maccabi Bnei Raina have not played in over six weeks.
Uruguay possible starting lineup:
Rochet; R Araujo, Caceres, Gimenez, Olivera; Ugarte, Valverde, De la Cruz; Pellistri, Nunez, De Arrascaeta
Bolivia possible starting lineup:
Viscarra; Quinteros, Haquin, Sagredo, Fernandez; Justiniano, R Vaca, Miguelito; H Vaca, Marcelo Moreno, Algaranaz
We say: Uruguay 4-0 Bolivia
Bolivia are awful travellers and are unlikely to cause much trouble to a Uruguay side full of confidence.
The hosts must avoid complacency in a clash they are heavily expected to win, as top spot could be theirs heading into 2024 if Argentina drop points against Brazil.
For data analysis of the most likely results, scorelines and more for this match please click here.
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