Spurs had to ride their luck at times in the remainder, with Toon debutant Salomon Rondon hitting the bar late on, but they held on for an opening-game win at this venue for the second year running.
Harry Kane was named in Tottenham's starting lineup despite only returning to training this week, but the England international failed to make much of an impact to see his goalless run in August stretch to a 14th match.
The first goal was awarded through the use of goal-line technology, as Vertonghen glanced in Davinson Sanchez's knockdown via the underside of the crossbar.
A third goal in the space of 10 minutes would swing the game back in Tottenham's favour, and it came from another teasing cross from out wide.
The contest then settled into more of a rhythm, with the next chance not arriving until the final six minutes of the half.
Sanchez ghosted past Jonjo Shelvey - sent off in this fixture nearly 12 months ago to the day - and flicked a left-sided corner inches wide of the far post, shortly before Ciaran Clark volleyed a half-cleared cross agonisingly wide at the other end.
Tottenham were given a wake-up call early in the second half as Mohamed Diame's thumping shot struck the near post, while Kenedy could not make the most of Ayoze Perez's outside-of-the-boot through-ball, with a heavy first touch giving Lloris a chance to close the angle.
Sanchez then volleyed over an empty net from a difficult angle, and Perez tested Lloris down low with his snapshot as the chances kept on coming at both ends.
Newcastle were the side asking all of the questions in a quieter final 15 minutes and were nearly rewarded with a late leveller.
Substitute Rondon took Shelvey's pass in his stride and got a shot away from the game's final chance, which looped off Vertonghen and hit the crossbar in a major let-off for the visitors.
NEWCASTLE UNITED (4-4-1-1): Dubravka; Yedlin, Lascelles, Clark, Dummett; Ritchie (Atsu 69'), Shelvey, Diame, Kenedy; Perez (Muto 81'); Joselu (Rondon 59')
TOTTENHAM HOTSPUR (4-2-3-1): Lloris; Aurier, Sanchez, Vertonghen, Davies; Dier (Amos 88'), Sissoko; Eriksen, Dele (Son 80'), Lucas (Dembele 68'); Kane