There was a spectacular flame display before kick-off, courtesy of the club's front-of-shirt partner Sela, and from the very beginning there were fireworks on the pitch too.
United took the lead in the sixth minute to heat things up even further; Bruno Guimarães had a shot parried by Emi Martínez, but Anthony Gordon recovered the loose ball, exchanged passes with Joelinton and then crossed from the left for Tonali to ghost into the box and volley home.
It meant that the Italian, the 258th player to represent the Magpies in the Premier League, became the fastest man to score for the club on his Premier League debut, overtaking Joe Willock - and Tonali could have had another moments later.
Gordon slid him in and the former AC Milan midfielder tried to pick his spot, but Martínez spread himself and was able to block.
In the ninth minute, Gordon made a key contribution at the other end. Moussa Diaby broke on the left but the ex-Everton youngster kept stride with the flying Frenchman, keeping him wide and forcing him into taking his shot from an angle that made it relatively comfortable for Nick Pope to save.
However Diaby matched Tonali's feat of scoring on his Premier League bow two minutes later as he brought the visitors level. Lucas Digne swung the ball over from the Villa left, Ollie Watkins flicked on and Diaby, a big money summer arrival from Bayer Leverkusen, finished well.
But United regained the lead in the 16th minute as Tonali's deep delivery was kept alive by the stretching Sven Botman and Isak diverted home from 12 yards. There was a thorough VAR check for offside, but the goal stood and the Magpies were ahead for a second time.
Villa had two presentable opportunities before the break, with Watkins dragging wide from Diaby's pass in the 24th minute before Diaby hit the side-netting in the 42nd minute after a one-two with Douglas Luiz.
Then, with ten minutes of added time due largely to an injury to Villa defender Tyrone Mings, there was a controversial moment shortly before half time when Martínez came rushing out of his goal to bring Miguel Almirón to the ground after the Paraguayan had knocked the ball past the Villa goalkeeper.
Referee Andy Madley felt that the the visitors had enough covering defenders to avoid showing a red card, meaning Martínez escaped with a booking, much to the displeasure of the home supporters and United head coach Eddie Howe.
But Howe and the majority of the 52,207 crowd were celebrating in the 58th minute when Isak outmuscled and outwitted Ezri Konsa and lofted a magnificent finish beyond Martínez to make it 3-1.
Two minutes later, from an Almirón through-ball, Isak raced in on goal again but this time was thwarted by Martínez, who also recovered to save from Almirón after his attempted clearance presented the Paraguayan with an opportunity.
In the 64th minute, Watkins saw a shot pushed away by Nick Pope and the onrushing Matty Cash blazed over the unguarded target, then ten minutes later the same player drilled a shot across goal which Pope did well to tip behind.
But with the Villa full-back unable to Cash in, it was left to substitute Wilson to add a fourth for the Magpies and get his customary opening day goal as he converted from a low cross from fellow substitute Harvey Barnes, making his competitive debut for the club, in the 77th minute.
He somehow failed to add to his tally in the 82nd minute when Barnes again supplied him, only for Martínez to deny him with a trailing leg, then Joelinton had an effort cleared off the line.
But in stoppage time, United got their fifth to go top of the table on the opening weekend. Jacob Murphy's pass allowed Barnes to race through to become the 14th Newcastle player to score on their Premier League debut, and the second of the day, as the magnificent Magpies made a hugely impressive start to the new campaign.
