The 27-year-old made 26 competitive appearances for French club Marseille last season, and played regularly for Argentina on their way to reaching the 2026 FIFA World Cup final.
Predominantly a left-back, Medina also provides defensive cover in central positions, and Leverkusen's second defensive signing after Miguel Gutierrez, who joined from Napoli.
Leverkusen sporting director Simon Rolfes said: "In Facundo Medina, we have signed a highly experienced professional who, thanks to his quality and strong mentality, will immediately be a key player for our team.
"He's a player who excels in one-on-one situations: assertive and aggressive. Facundo's qualities add an important element to our squad's profile. We're delighted to have him in our ranks."
Medina played four games at the 2026 FIFA World Cup, including coming on as a substitute in the final, as Argentina finished runners-up to Spain following a 1-0 defeat.
"Making the move to Bayer 04 in the Bundesliga is fantastic for me," said Medina. "At the World Cup in North America, Exequiel Palacios told me a lot about the club and spoke very highly of Leverkusen.
"Pala has been here for so long and has enjoyed great success – that's something I'd like to experience with Bayer 04 too."
Newly-promoted Schalke claimed their first Bundesliga victory since the 2022/23 season with an impressive 3-1 win at Union Berlin, extending their unbeaten record at Stadion An der Alten Forsterei and moving into the top half of the table.
Bayern Munich began their Champions League campaign in emphatic fashion as Jamal Musiala and Michael Olise inspired a 5-0 victory over Bodo/Glimt on Thursday.
Como marked their first-ever Champions League appearance in spectacular fashion as they swept aside RB Leipzig 4-1 at the Stadio Giuseppe Sinigaglia on Thursday.
Victor Boniface's uncertain situation at Bayer Leverkusen has taken another intriguing turn after the Nigerian striker wiped his Instagram account and posted a cryptic message thanking God for standing by him.
