NFL executive vice president Peter O'Reilly said at Thursday morning's (AEDT) announcement that the league has not settled on when the match will be played in 2026, but it could be in week one of their season.
Given the NFL starts in the first week of September, that would mean it comes up against the opening round of the AFL's finals series.
Next year's game will be the first time the NFL has played a regular-season game in the Asia-Pacific region.
The Los Angeles Rams have been confirmed as the host team and their opposition will reportedly be the Philadelphia Eagles.
It is a multi-year deal as the league continues its international expansion.
"Expanding to Melbourne, a beautiful city with a rich sports history, underlines our ambitions to become a global sport and accelerate international growth," NFL commissioner Roger Goodell said.
"Together with the Victorian State Government ... we look forward to making history in what is an important market for the NFL and a significant next step in expanding our international footprint."
The announcement was made in New Orleans, host city of the Super Bowl next Monday morning.
Eagles offensive tackle Jordan Mailata will become the first Australian to play in a winning Super Bowl team if they beat the two-time defending champion Kansas City Chiefs.
Philadelphia narrowly lost to the Chiefs in the Super Bowl two years ago.
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