Darwin Nunez and Nicolas de la Cruz scored to give Uruguay a 2-0 win over Brazil in their 2026 World Cup qualifier on Tuesday as Neymar was forced off late in the first half after suffering what appeared to be a serious knee injury.
Nunez opened the scoring in the 42nd minute with a diving header, and Brazil's night went from bad to worse two minutes later when Neymar went down after tussling for the ball with De la Cruz.
Visibly distressed, Neymar left the pitch on a stretcher after receiving treatment for several minutes.
Brazil FA sources said the forward had sustained a severe left knee sprain and that he would undergo tests to determine if there was ligament damage.
"Let's hope it's nothing serious," Brazil captain Casemiro told Globo television.
"He's an important player for us, we're very fond of him. He's been suffering a lot from injuries and when he starts to pick up the pace he gets injured again."
Brazil had much of the possession in a dour first half but had nothing to show for it, and Uruguay took the lead with the first shot at goal in the match.
Maxi Araujo received a quick throw-in and got in behind Brazil defender Marquinhos before crossing for Nunez to score.
Uruguay remained on top after the break and De la Cruz extended the hosts' lead with a close range effort in the 77th minute, with Nunez providing the assist after winning a challenge against two Brazilian defenders inside the box.
It was Uruguay's first win over Brazil since 2001.
Brazil ended the match with no shots on target and suffered their first defeat in a World Cup qualifier since 2015 after going 37 games unbeaten.
The victory lifted Uruguay to second in the CONMEBOL standings on seven points, level with Brazil and Venezuela, who beat Chile 3-0 earlier on Tuesday.
Paraguay earned their first win in the South American qualifiers as they beat bottom side Bolivia 1-0 in Asuncion, while Ecuador were held 0-0 by Colombia.
Leaders Argentina are also in action against Peru on Tuesday.