Roethlisberger's 45-yard TD strike to wide receiver Diontae Johnson gave Big Ben the milestone mark of 400 career touchdown passes.
Roethlisberger is just the eighth quarterback all time to throw 400 or more TDs.
Unfortunately for Roethlisberger and the Steelers, it was his only TD throw of the game, which Pittsburgh lost, 27-17. Roethlisberger was 27-for-40 passing for 232 yards, the touchdowns and an interception as the Steelers (1-3) lost their third in a row.
Roethlisberger now also has 61,381 yards passing, which passed Dan Marino's 61,361 for sixth on the all-time list.
Roethlisberger found the end zone on the opening drive of the game, hitting Johnson in stride with a deep shot on a free play after the Packers jumped offsides.
Sitting at 399 entering Sunday's game, Roethlisberger ascended into the elite 400 club against an unfamiliar foe in the Packers, whom the Steelers signal-caller had previously played against in just three regular-season games, though he had nine touchdowns in those games.