The announcement was made on Saturday, signalling the start of a new era for the Bundesliga side following the summer departure of Xabi Alonso.
Tillman, a 22-year-old attacking midfielder, enjoyed considerable success during his time in the Netherlands, helping PSV clinch the Eredivisie title in each of the past two seasons.
His consistent performances caught the attention of Leverkusen's new boss, who has moved swiftly to bring him in as part of his squad revamp.
Born in Germany to a German mother and American father, Tillman holds dual nationality but represents the United States at international level.
He has already earned 25 caps for the US men's national team and recently featured in six matches during this summer's CONCACAF Gold Cup.
Tillman's football journey began at Greuther Furth, before joining Bayern Munich's academy in 2015. He progressed through the Bavarian club's youth ranks, developing a reputation as a technically gifted midfielder with a sharp eye for goal.
His move to Bayer Leverkusen marks a return to his homeland and a new challenge under the guidance of a manager known for nurturing young talent.
With Champions League football and domestic honours in sight, Tillman will be aiming to play a pivotal role in Leverkusen's ambitions this season.