Canada won their first tie 22-21 a week ago but Saturday's drubbing in Valparaiso, Chile, kept the home team's dream alive to compete at the Rugby World Cup 2023.
"This is a hugely disappointing result - although we remain proud of the staff and players and the efforts they made over the past months, we all know the expectations for Canadian rugby are rightfully higher," Rugby Canada CEO Allen Vansen said in a written statement.
Chile will face the United States in a two-legged tie next year to decide which team will feature in France 2023.
Uruguay qualified after defeating the US 34-15 on Saturday for a 50-34 aggregate score, reaching their fifth Rugby World Cup.
They'll join New Zealand, France and Italy in Pool A, with a final qualifier from Africa yet to be decided.
Photo Twitter/Rugby Canada