Harvey Barnes struck twice in the second half as Newcastle put Manchester United to the sword at St James' Park.
Sandro Tonali gave Toon the lead after 24 minutes with a well-struck volley but United went into the break even after Alejandro Garnacho equalised.
However, two goals from Barnes and a contribution from Bruno Guimaraes ensured a dominant win for Newcastle - even if the visiting fans chanted Ruben Amorim's name until the end.
Newcastle boss Eddie Howe missed the match due to being in hospital, with his assistant Jason Tindall taking the reins in impressive fashion.