Uruguay got past Peru 1-0 after Giorgian De Arrascaeta’s 42nd-minute strike, which proved enough for the home side in Montevideo.
Ecuador went down 3-1 in Paraguay but clinched their berth by virtue of fifth-placed Peru’s loss.
Peru are four points adrift of Uruguay in fourth with one game to play. The top four sides qualify automatically while fifth will need to progress via the playoff.
The Peruvians are on 21 points, ahead of Colombia (20) and Chile (19).
Uruguay have now qualified for four straight World Cups, led by Luis Suarez and Edinson Cavani in attack. La Celeste dismissed long-term boss Oscar Tabarez in November with Diego Alonso finishing the job.
Alonso said: “We are not going to go to the World Cup to participate, but we have to go to give our best.
“I am happy, excited about what happened today, but above all things with the peace of mind of having fulfilled my duty. The team unites and we Uruguayans are proud.”
Ecuador’s qualification is their first since 2014, having also reached the World Cup in 2002 and 2006.