The game, which is the first of three regular-season fixtures taking place in London this season, will see the Manchester-born tackle play in his home country.
The 25-year-old, who was a second-round Draft pick in 2013, told the team's website: "As a kid, we all had dreams to play in the Premier League and stuff. Playing in the FA Cup in Wembley was always something you dreamed of as a kid.
"I watched the Steelers out here last year versus Minnesota and then I didn't really think until the schedule came out. It's like a dream really.
"So, it's surreal, and my teammates are excited. Hearing them talk and of them trying to do their English accents is fun. It's a moment I'll remember forever."
Watson only took up gridiron in 2011 after spending his first two years in college focused on basketball.