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.
Manchester City secured a second successive Premier League victory at home against Sunderland, Chelsea were held scoreless away to Bournemouth while Tottenham managed to beat Brentford.
Aston Villa delivered a major jolt to the Premier League title race as Emiliano Buendía struck deep into stoppage time to seal a 2-1 win over Arsenal on Saturday.
David Moyes urged Everton to stay on the front foot as they prepare for Saturday's Premier League meeting with Nottingham Forest at Hill Dickinson Stadium, where Sean Dyche made his first return since leaving the club nearly a year ago.
Mikel Arteta has said that Aston Villa's blistering run of form has made them genuine contenders in the Premier League title race, as Arsenal prepare for a high-stakes trip to Villa Park.
