It was the Seagulls first game in the top flight for 34 years and a new record crowd of 30,415 packed out the Amex as the home side held their star-studded rivals for much of the contest.
But two goals in the last 20 minutes, the first from Sergio Aguero and the second a Lewis Dunk own goal saw Pep Guardiola's side get off to a winning start in a day of shocks in the Premier League.
City dominated possession with 77 per cent in a first half in which Albion had just one shot and went on to see 78 per cent of the ball throughout the 90 minutes.
But the home side defended superbly and were well organised for much of the contest against the league's big spenders, but in the end quality told in what was a historic and emotional day for the club.
Albion featured five of their summer signings with goalkeeper Mathew Ryan, Pascal Gross, Davy Propper, Markus Suttner and Izzy Brown handed their full debuts with the Anthony Knockaert only making the bench on his injury return.
With it all change in the transfer market, only three players - Lewis Dunk, Bruno and Dale Stephens - that started in the Seagulls' final game of the promotion-winning season got the nod to lead them into the Premier League.
City handed debuts to three new additions in goalkeeper Ederson and two of their big-money full-backs in Kyle Walker and Danilo, while their bench value stood at a staggering cost Â£200.4m.
The atmosphere was electric at kick-off and a lively start just added to the fever pitch with the Amex basked in glorious sunshine. City had the first real opportunity on five minutes as an excellent block by Shane Duffy denied David Silva a tap in after a quick break by Gabriel Jesus.
The visitors went on to dominate possession and move the ball around sharply, but were limited to few chances despite the darting movement of Sergio Aguero and Jesus causing problems.
Albion were hit by a blow on 22 minutes as Brown went down with what looked like a hamstring problem and limped off to be replaced by Jamie Murphy.
City had the ball in the net just before the half-hour mark as Jesus put in De Bruyne's cross but the effort was ruled out as it hit the City striker's chest and then hand - deemed deliberate as he was booked - before he collided with Ryan.
The best chance of the half came on 33 minutes and City should have led as Jesus' header produce a fine point-blank left-handed save from Ryan and the striker put the follow-up wide.
Albion's only chance of the first 45 minutes came just before the break as Murphy was unable to control a Dale Stephens ball over the top and Ederson collected the loose ball.
The one-way traffic continued after the break as Jesus again had the ball in the net, rolling home after a square pass from Silva, but the midfielder was offside from a dinked pass over the top. Aguero then fired well wide as he raced through on goal thanks to a short back pass from Duffy.
Albion then got in on the act as Murphy raced away down the left and and Markus Suttner's cross was headed behind for a corner, before from the resulting flag kick Duffy's short was deflected just wide. Lewis Dunk then had two efforts blocked after an Ederson fumble and Propper flashed the follow-up wide.
But it was the City pressure that told on 69 minutes as Stephens lost possession on the halfway line and City broke quickly, with Silva finding Aguero, who fired home.
It was 2-0 six minutes later as Fernandinho crossed from the right and Dunk, under pressure from Jesus, headed into his own net from six yards.
Chris Hughton turned to Knockaert as he replaced Solly March to accompany Glenn Murray in the attack, who had earlier come on for Tomer Hemed. It did not make much difference as City closed out the remaining minutes with few chances to note for either side.
Albion: Ryan, Bruno, Dunk, Duffy, Suttner, Brown (Murphy 22), Gross, Propper, Stephens, March (Knockaert 75), Hemed (Murray 59). Unused subs: Huenemeier, Sidwell, Rosenior, Maenpaa.
City: Ederson (Sane 67), Walker, Kompany, Stones, Oteamendi, Danilo, De Bruyne, Fernandinho, D.Silva, Jesus, Aguero (B.Silva 82). Unused subs: Sterling, Mangala, Toure, Foden, Bravo.
Referee: Michael Oliver.