The Manchester City forward is set to face his country of birth in a World Cup showdown that could go a long way towards deciding who progresses from Group L, with both England and Ghana opening their campaigns with victories.
For Semenyo, however, there is no conflict of emotions. Representing Ghana has always been a source of pride, and he says the decision to commit to the Black Stars was one of the easiest he has ever made.
Speaking to Football Presse in his role as Ahmad Tea's new Global Brand Ambassador, Semenyo reflected on accepting Ghana's call-up.
"I got a call from Ghana when I was 20 or 21, I could never say no to that. I've already got to represent my country at a World Cup and now I'm heading into my second one," he said.
"I was never in the England underage teams so never thought of it as a possibility. My family also love Ghana, they all support them. My dad was so proud when I played for Ghana.
"I'm creating memories playing for a country that means a lot to me. It was an easy decision back then and one I'm proud of today."
Now preparing to take on England on football's biggest stage, Semenyo knows exactly what the Three Lions face every time a major tournament comes around.
Having grown up in England, he witnessed first-hand the enormous expectations that follow the national team whenever World Cup or European Championship campaigns begin.
"Massively. Every major tournament, you hear the noise. 'Will this be the one to end the years of hurt?' and the media coverage is insane. That's a lot of pressure but it is similar for other countries too."
England arrived at the tournament among the favourites, boasting one of the deepest squads in world football. Yet Semenyo believes Ghana are capable of producing one of the shocks of the competition.
"Can they? Of course. They've got some sensational players and can go all the way. Will they? It's tough as there are so many talented players and so many competitive nations. I hope Ghana can stop them."
A victory over England would rank among the biggest results in Ghana's recent history and potentially move the Black Stars to the brink of qualification for the knockout rounds.
Semenyo believes such a result would send a powerful message to the rest of the tournament.
"Huge. As I said, we believe we can give anyone a game and to go out there and beat a team like England would send a real message that we mean business at the World Cup," he said.
"It will be difficult, they're one of the favourites, but we have a good team and nothing is impossible."
The occasion will also bring an added layer of familiarity for Semenyo, who expects to line up against several players he knows well from club football.
"I've told Nico [O'Reilly], Marc [Guehi] and John [Stones] I'm coming for them!" he joked.
"There will probably be some banter in the build up to the game and it will be great to go up against them. Obviously I've played against them for Bournemouth before and trained so much with them at City now so I know what to expect but this is a whole new stage.
"It will be great to see them, James [Trafford] is obviously in the squad too, but as close as we are, I'm playing to win. As I'm absolutely certain they will be too."
Friendships will be put to one side when the whistle blows. For Semenyo, tonight's clash is about helping Ghana prove they belong among the world's best — and delivering a statement result against one of the tournament favourites.
Antoine Semenyo is the new Global Brand Ambassador for Ahmad Tea, one of the world's leading family-owned tea companies. For more information about Ahmad Tea and its commitment to quality, craftsmanship and sustainability, visit www.ahmadtea.com.