Facundo Pellistri nodded home the opener in the eighth minute and Darwin Nunez doubled Uruguay's lead just after the 20-minute mark, powering a left-footed shot past Bolivia keeper Guillermo Vizcarra.
Maximiliano Araujo struck from close range to kill off the contest in the 77th minute, before Federico Valverde made it 4-0 four minutes later.
Substitute Rodrigo Bentancur completed the rout by heading home the fifth in the 89th minute with his first touch.
Uruguay will progress as group winners if they avoid defeat by the United States in their final group game on Monday (Tursday AEST), but even defeat in that match would likely see them go through thanks to their superior goal difference.
Panama's Jose Fajardo scored the winner as his side beat the United States 2-1 in Atlanta. (AP PHOTO)
In the earlier game in Atlanta, Panama struck late to beat the United States 2-1 in their Group C match, after the hosts were forced to play most of the match with 10 men.
US defender Timothy Weah was sent off in the 18th minute for lashing out at Roderick Miller, but Folarin Balogun gave the hosts the lead with an emphatic strike from just outside the box four minutes later.
Panama equalised in the 26th minute, when Cesar Blackman beat Matt Turner to the keeper's right with a low shot from the top of the box.
Substitute Jose Fajardo smashed home Abdiel Ayarza's cross in the 83rd minute to secure the win in Atlanta.
Panama were also reduced to 10 men after Adalberto Carrasquilla was sent off in the 88th minute for a crunching tackle on Christian Pulisic.
The win moved Panama level on three points with the United States.
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