Albion have not revealed what the "multi-year agreement" is worth but chief executive Paul Barber has described the deal as the biggest in the club's history.
The agreement will see the American Express logo adorn the front and back of the first-team's new shirt, which is set to be unveiled on Wednesday and will go on sale to supporters in the summer.
The American Express logo will also be prevalent on the club's development, youth and women's team shirts, with the US company already holding naming rights for the Seagulls' Amex Stadium.
Barber told Brighton's official club website: "American Express has proven to be a fantastic partner as our stadium naming rights holder and key partner of our charitable arm, Albion in the Community.
"To see one of the world's biggest and most respected companies extend its relationship with us in this way, cementing its position as the club's main sponsor, is fantastic news for us.
"This is a significant deal for the club and the biggest in our history.
"We are extremely grateful to American Express for its continued support. I would like to thank them for the invaluable expertise, assistance and advice they have provided to our club since the stadium opened, something that only a truly global brand can offer."