The Portuguese coach, appointed at the end of September, celebrated his first league victory in charge of the Hammers after a spirited display that saw them climb one place to 18th in the table, though they remain in the relegation zone.
West Ham made a poor start, conceding in the fourth minute when Jacob Murphy fired Newcastle ahead. But Lucas Paqueta restored parity in the 35th minute before an own goal from Sven Botman completed the turnaround in first-half stoppage time. Tomas Soucek sealed the win deep into stoppage time, sparking loud celebrations around the ground.
Nuno praised his players' effort and hailed the home support after finally giving fans something to cheer about. "The players are realising that winning in the Premier League, we have to work very hard," he said.
"The win makes it easier, there are smiles and the legs feel lighter. We are seeing improvements on the pitch, and this means a lot for the club and our fans. The noise today was terrific."
The former Nottingham Forest and Wolves manager added: "Our idea is to give something back to our fans, and today we did. The way they responded was incredible. Let's try against Burnley to give them even more, to make the London Stadium a very difficult place for our opponents."
For Newcastle, it was another miserable outing away from home. Eddie Howe's men are still without a league win on the road this season, now winless in eight away games, and looked short of intensity after their early breakthrough.
"I can't really defend the performance," Howe admitted. "After that start, I thought we could control the game, but we didn't. We let West Ham in with some uncharacteristic errors.
"It was a poor display, and we need to find consistency."
The victory gave Nuno's side renewed belief ahead of their upcoming home clash with Burnley, while Newcastle face pressure to rediscover their form away from St James' Park.
Roberto De Zerbi wants Tottenham Hotspur to turn the fighting spirit they showed against Manchester United into a stronger team as they prepare for their next Premier League match.
Morgan Rogers has credited Xabi Alonso's team talks for Chelsea's impressive starts to matches this season after the Blues raced to a 5-1 victory over Bournemouth at Stamford Bridge.
Manuel Akanji has admitted he is unsure what will happen to Manchester City's trophies following the club's guilty verdict over financial rule breaches, but the Inter Milan defender hopes he will get to keep his titles.
Michael Carrick has praised Mikel Arteta for building a successful team at Arsenal but admitted that the Spaniard's achievements are difficult to celebrate because of Manchester United's historic rivalry with the Gunners.
