Sao Paulo's Corinthians Arena - home to Serie A side Corinthians - will welcome the AFC West side to South America on the first week of the campaign, scheduled for Friday, September 5th.
The Chargers, who finished with an 11-6 record in the 2024 season, bowing out to the Houston Texans in the playoffs, will become the first team to play on five different continents when they touch down in Brazil.
"It's an honour to once again represent the NFL on an international stage," said Chargers President of Business Operations A.G. Spanos.
"It's also a tremendous opportunity to help grow the game and bring the Chargers brand to millions of sports fans across Brazil and Latin America. One of the great countries of the world, Brazil is as vibrant, dynamic and culturally diverse as anywhere on the planet, and we cannot wait to experience the warmth and passion of its people during our visit."
Their opponent will yet to be confirmed with the 2025 schedule to be released later this spring.
Brazil became the next in a long list of countries to host a regular season game in 2024. Alongside them for the next season, the UK, Republic of Ireland, Spain, Germany and Mexico will all host other NFL fixtures, whilst Melbourne will host one in 2026.
Last season's match-up in Sao Paulo saw eventual Superbowl champions, the Philadelphia Eagles beat the Green Bay Packers 34-29.