West Ham United capitalised on two mistakes by new Arsenal new goalkeeper Petr Cech to claim a surprise 2-0 Premier League victory at the Emirates and leave the Gunners deflated.
Philippe Coutinho's stunning late strike gave Liverpool a 1-0 victory at Stoke City to avenge their 6-1 defeat at the Britannia Stadium on the final day of last season.
Steve McClaren's reign as Newcastle United manager began with a 2-2 home draw against Southampton.
Arsenal, full of opening-weekend optimism, knew the importance of a good start to the season after five draws and a defeat in the first eight games of the last campaign left them too far behind eventual champions Chelsea.
Victory over Chelsea in the Community Shield fuelled hopes that Arsene Wenger's side could improve on last season's third place but goals from Cheikhou Kouyate and Mauro Zarate earned West Ham victory in Slaven Bilic's first league game in charge.
Arsenal were booed off at the final whistle with Cech culpable in both West Ham goals.
The former Chelsea keeper was signed during the close season to shore Arsenal up defensively but the experienced Czech had a day to forget in the north London sunshine.
Just before half-time he came flying out to punch Dimitri Payet's free kick but was beaten to the ball by the head of Kouyate. Twelve minutes after the restart Zarate's low strike sneaked past him at the near post.
West Ham, who gave a Premier League debut to 16-year-old midfielder Reece Oxford, were deserved winners.
"We are all very pleased and it is great start for us. Not only for the three points but points against a team that are the title contenders," former West Ham player Bilic said.
"If you add to that a London derby, it makes it an even bigger win. This is very special."
Wenger described the result as an accident.
HURT MENTALLY
"We know fitness wise, West Ham were ahead of us, they had already played competitive games (in the Europa League). You never get the same intensity," the Frenchman said.
"Today we have been hurt mentally and it is a good opportunity to respond."
Arsenal went close early on through an Alex Oxlade-Chamberlain volley before Aaron Ramsey's deflected strike hit the top of the crossbar.
But West Ham, knocked out of the Europa League in the third qualifying round by Romanian side Astra Giurgiu on Thursday, snatched the lead in the 43rd minute when Kouyate made the most of Cech's error of judgement.
Arsenal lacked urgency after the break and Oxlade-Chamberlain's casual defending was punished by Zarate who stole possession and fired a shot past the flat-footed Cech.
Intense late pressure from the hosts was comfortably dealt with by West Ham's defence.
As Newcastle boss McClaren stepped foot in a dugout as a Premier League manager for the first time since 2006, his opposite number Ronald Koeman was nowhere to be seen after undergoing an operation for a ruptured Achilles.
The Saints seemed unaffected by his absence, however, and took the lead in the 24th minute when Italian striker Graziano Pelle rose high to plant a header past Tim Krul.
Newcastle equalised just before half-time through Papiss Cisse and new signing Georginio Wijnaldum headed in Gabriel Obertan's perfectly weighted cross to swing the advantage in the hosts' favour before Shane Long levelled in the 79th minute with another header.