Uruguay advanced on 25 points, four ahead of fifth-placed Peru, which went down to Giorgian De Arrascaeta's goal late in the first half and couldn't find a way back.
There was scant goalmouth action in Montevideo, but Federico Valverde twice came close to scoring a long-range screamer, his second-half effort crashing into the crossbar with furious force.
Peru is still in control of its play-off fate, although both Colombia and Chile can catch it as Paraguay will attempts to play the role of spoiler in next Wednesday's (AEDT) final match in Lima.
Ecuador also qualified on Friday (AEDT), despite a 3-1 defeat to Paraguay, thanks to Uruguay's victory over Peru.
La Tri, which failed to make Russia 2018, knew it needed only a point to be sure of a top-four finish with a game to spare.
However, already-eliminated Paraguay was clinical at Ciudad del Este, and was 3-0 up before the hour mark through Robert Morales, a Piero Hincapie own goal and Miguel Almiron.
Ecuador threatened a dramatic fightback as Jordy Caicedo scored a late penalty and Blas Riveros was sent off, but ultimately its fate was decided by events in Montevideo.
Colombia kept its hopes alive with a 3-0 win over Bolivia, Luis Diaz, Miguel Borja and Mateus Uribe scoring the goals.
Peru, which occupies the crucial fifth spot on the CONMEBOL ladder, remains the favourite to seal that play-off spot and will do so with victory over Paraguay next week. Colombia, in sixth place, faces Venezuela while Chile must beat Uruguay and hope other results go its way if it wants to be in the mix.