Defeat left Leicester third, two points in front of Chelsea and five ahead of West Ham, with both London clubs having a game in hand over the Foxes.
This reverse came five years to the day since Leicester received the Premier League trophy, having started the 2015/16 season as 5,000/1 rank outsiders to be crowned English champions.
Newcastle's win saw them move 12 points clear of the relegation zone, just one shy from safety with three games remaining.
Joe Willock, on loan from Arsenal, fired Newcastle in front in the 22nd minute at the King Power Stadium as he scored in his fourth successive top-flight game for the Magpies.
And the visitors doubled their lead before half-time with a rare goal from Paul Dummett.