Two goals from Chris Zebroski and efforts from Harry Worley and Christian Jolley ensured Accrington Stanley manager James Beattie's first competitive match as a manager ended in defeat at Rodney Parade.
Danny Webber scored to pull one back for for the Reds but Newport were deserved winners in a fairytale start for the Welsh side, playing in the Football League for the first time in 25 years.
Newport started strongly and the Exiles had the ball in the net in the fifth minute after a goalmouth scramble, but Jolley's effort was disallowed for handball by referee Darren Drysdale.
Stanley responded well two minutes later after debutant Webber flicked on a cross into the path of Peter Murphy, but the midfielder was thwarted by a last ditch tackle.
The hosts continued to press, and there was a nervous moment for goalkeeper Ian Dunbavin in the 12th minute after he spilled an innocuous cross from Zebroski in the box, but Nicky Hunt did well to clear.
Despite a vociferous home crowd, Stanley created some fine passing moves which included an excellent exchange between Webber and Will Hatfield, but the former Manchester United striker's shot was superbly blocked by Ismail Yakubu – nephew of Yakubu Aiyegbeni, the former Everton and Portsmouth striker.
But the Exiles deservedly broke the deadlock after 23 minutes as a long throw from Adam Chapman was poorly dealt with inside the box and Worley duly stabbed home a left-foot shot.
Moments later, with the Reds visibly rattled, Newport should have added a second but Yakubu inexplicably headed wide from three yards.
Stanley then began their most threatening period of play and should have levelled in the 36th minute after a delightful chested pass from Lawrie Wilson found Webber free inside the six-yard box, but his touch was too heavy and his shot was well blocked by goalkeeper Jamie Stephens.
In the 42nd minute Newport doubled their advantage after a dangerous low cross from Jolley was fired in by debutant Zebroski to the delight of the lively County fans, but the goal was a cruel blow to Stanley who looked the likelier to score.
Beattie's first ever half-time team talk did not appear to do the trick as Newport added a third in the 55th minute. Exiles chairman Les Scadding funded the signing of Jolley himself, and the striker repaid his boss as he tricked his way onto the edge of the area before he curled in a beautiful effort past Ian Dunbavin.
Ten minutes later Zebroski fired in his second of the game with a fantastic dipping volley from inside the area that was too powerful for Dunbavin in goal.
The Reds did pull a goal back to muted celebrations after a cross from substitute Luke Clark was touched on by Murphy before the ball fell to Webber who calmly netted a consolation on his debut for Stanley.
Stanley: Dunbavin, Liddle, Aldred, Atkinson, Hunt, Hatfield (Carver, 60), Murphy, Joyce (Clark, 65), Richardson, Wilson, Webber (McCartan, 80).