Suárez made his senior debut for Uruguay on Feb. 8, 2007 in a 3-1 victory against Colombia and soon became an integral part of the squad. By 2010, he featured in 19 of the 20 World Cup qualifying matches to secure a spot for La Celeste at the tournament in South Africa.
The forward played a pivotal role in his first of four World Cups, starting five of Uruguay's six matches. During the quarterfinal against Ghana, Suarez committed an infamous handball in the final moments of the game, giving Ghana the chance to win the game with a penalty. Though Suárez was sent off, Asamoah Gyan missed the attempt and Uruguay went on to win the match via a penalty shootout and advance to the semifinals.