First-half goals from striker Andy Carroll and winger Wayne Routledge sealed a victory that prompted jubilant away fans to invade the pitch at the final whistle.
The Plymouth faithful were anything but celebratory, however, after defeat confirmed their relegation to League One with two games left.
Newcastle – owned by sports retail mogul Mike Ashley – had already ensured their return to the top flight at their first attempt and needed just a point to go up as champions.
Carroll (left) put them in front after 20 minutes when he headed in Joey Barton’s corner. Barton also laid on the second for Routledge to finish from a tight angle eight minutes later.
Manager Chris Hughton praised his team’s fans, who made the epic 410-mile journey from the north east to Devon. He said: “We’ve had magnificent support and they’ve made every stadium we’ve gone to.”