The Los Angeles Rams will be the home team when they face the Kansas City Chiefs on Monday Night Football from Mexico City on November 19, the NFL has announced.
The announcement came ahead of the release of the full 2018 regular-season schedule on Thursday.
The Rams-Chiefs game at Estadio Azteca will be the league's second Monday night contest in Mexico City. The Raiders and Houston Texans met there in 2016, with Oakland winning 27-20.
For the Chiefs, it will be the franchise's first trip to Mexico since a preseason contest in Monterrey in 1996.
The Rams have never played in Mexico, which has played host to 10 NFL games.
The NFL will have three other International Series games in 2018, all of which will take place in London in October.
The Seattle Seahawks will take on Oakland Raiders at Tottenham's newly developed stadium on October 14.
Super Bowl champions, the Philadelphia Eagles, will face the Jacksonville Jaguars at Wembley on either October 21 or October 28. The Tennessee Titans will play the San Diego Chargers at Wembley on the alternate weekend. Dates for those two fixtures will finalised on Thursday.