Lyon will receive up to €33.6m for the player, including €4.1m in potential bonuses, according to figures published by the French club. Lyon have also retained a 10% sell-on clause, while Moreira's former club Sporting Lisbon will receive 20% of the fee under an agreement from his previous transfer.
Bayer Leverkusen sporting director Simon Rolfes praised the forward's profile in a statement.
"Afonso Moreira is a fast, agile and tricky attacker with a good finish and an excellent eye for his team-mates," Rolfes said.
"His pace and intense style of play fit excellently with our team. With Afonso, we gain additional firepower and creativity in the attacking third.
"We're looking forward to a hugely exciting and developable player in the shirt of our Werkself."
Moreira enjoyed an outstanding season at Lyon, scoring eight goals and providing 11 assists in 37 competitive appearances across all competitions. The Portugal Under-21 international had also been monitored by Manchester United among other clubs.
Speaking about his decision to join Leverkusen, Moreira explained what convinced him to make the move.
"The people in charge showed me, in conversations full of appreciation, a clear perspective, engaged intensively with my situation and my goals, and made clear they firmly believe in my potential," Moreira said. "That recognition meant a lot to me and was a key reason for my decision in favour of Leverkusen."
The signing represents a significant piece of business for Leverkusen as they continue to reshape their squad following a summer of departures, with Moreira's combination of pace and end product seen as a direct boost to the attacking options available to new head coach Carles Martinez Novell for next season.