A superb hat-trick from China-based midfielder Paulinho powered Brazil to a 4-1 drubbing of the Uruguayans in Montevideo to leave the five-time world champions all-but-certain of a place at next year’s finals in Russia.
The Brazilians now lead the 10-team round-robin competition by seven points after their latest win.
The top four teams in the standings qualify automatically and with only five rounds remaining, it would take a freakish set of results to deny Brazil.
Uruguay had taken the lead after only nine minutes when Brazil goalkeeper Alisson brought down Paris Saint-Germain striker Edinson Cavani for a penalty.
Cavani got to his feet and drilled the spot-kick beyond the Brazilian goalkeeper to put Uruguay 1-0 up.
But Paulinho produced a thunderbolt 10 minutes later, uncorking a screamer into the top corner from 25 yards to level at 1-1.
The midfielder then stabbed home Philippe Coutinho’s shot in the 51st minute to make it 2-1.
Sublime
Barcelona superstar Neymar added a third with a sublime chip in the 75th minute to effectively settle the contest.
Paulinho completed his hat-trick in injury time, turning in a low cross with his chest to cap a fine display.
Uruguay, who were missing the suspended Luis Suarez, remain in second place in the standings.
In Buenos Aires, Argentina had entered their clash with Chile desperately needing to take all three points to revive their campaign.
And captain Messi duly delivered when it mattered as Argentina avenged last year’s Copa America Centenario final defeat to the Chileans with a 1-0 win.
Messi stroked home his penalty on 16 minutes after veteran Chile defender Jose Fuenzalida brought down Angel Di Maria with a clumsy challenge.
Last year, Messi was left distraught after missing his penalty in the shootout at the Copa America Centenario in New York.
But the diminutive maestro made no mistake on Thursday, drilling his spot-kick beyond former Barcelona teammate Claudio Bravo to secure a vital three points for the two-time world champions.