Virgil van Dijk’s header was the difference between the two sides – Jürgen Klopp’s current and former – in the first half at the Bank of America Stadium, where 55,447 fans were in attendance.
The Reds had the upper hand in the early stages of the second period, Sheyi Ojo hitting the bar, but Christian Pulisic won and converted a penalty to level and then slotted home another goal one minute from the end.
Jacob Bruun Larsen added a third for Dortmund with a close-range finish in stoppage-time to inflict a harsh scoreline on Klopp’s men.
Liverpool survived a fourth-minute scare when Loris Karius came out of goal to retrieve a ball over the top but found Maximilian Philipp with his attempted clearance.