Weigl - who returned to first-team training last month - completed 45 minutes of the 3-2 win over Rödinghausen.
"It was a great feeling to be playing again," the 22-year-old midfielder told BVB total! "The ankle held up, we won - I'm delighted."
Despite his absence, Die Schwarzgelben top the 2017/18 Bundesliga standings after three matches.
Dortmund's deadline-day summer signing Jadon Sancho also featured against Rödinghausen, chipping in with a debut assist for the opening goal.