The Magpies had equalled a club-record 10-match losing start to a league campaign at Southampton last time out and their hopes of stopping the rot were hampered by a series of injuries on Saturday, but Ayoze Perez's goal proved enough for a vital victory.
Yoshinori Muto, captain Jamaal Lascelles and Jonjo Shelvey all hobbled off, with Matt Ritchie among those also struggling, before Perez - jeered by supporters in the side's last home game - netted a fine header.
With Watford ultimately punished for numerous missed chances in a one-sided first half, Rafael Benitez's Newcastle clung on to climb out of the bottom three.
Newcastle have repeatedly given up cheap goals from set-pieces at home this season and that theme almost continued as Adrian Mariappa was left unmarked and prodded narrowly wide.
A corner at the other end then led to an even clearer Watford opening. The visitors broke at pace and freed Gerard Deulofeu but, having already passed up one opportunity, he missed the target.
Martin Dubravka made a crucial stop from Isaac Success on the stroke of half-time, before Roberto Pereyra crashed an effort against the crossbar shortly after the restart.
But Watford were made to pay for their profligacy and Ki Sung-yueng's storming free-kick was flicked home by Perez, before Salomon Rondon headed wide when he might have added a second.
It did not cost Newcastle, though, and a brave defensive performance in the closing stages sealed the points.
What does it mean? Magpies finally back on track
The excuse of a gruelling fixture list had long since abandoned Newcastle, with home defeats to Leicester City and Brighton and Hove Albion leaving the locals worried. But at long, long last, Perez got the Magpies' season up and running. They will require more victories to pull clear of danger, but this was a start.
Substitutes save Benitez's men
Newcastle looked out of their depth prior to the withdrawals of Muto, Lascelles and Shelvey, yet they improved in their absence. Perez netted the crucial goal and responded to his critics by celebrating with his fingers in his ears, while Fabian Schar was a solid presence and Ki turned in his best performance in a black-and-white shirt.
43% - Three of Newcastle's seven Premier League goals this season have been scored by substitutes (43%). Impact. #NEWWAT— OptaJoe (@OptaJoe) November 3, 2018
Deulofeu costs Hornets the points
Watford dominated the first half and could have been out of sight had Deulofeu, starting in a central striking role, not forgotten his shooting boots. Twice he was unmarked in the area and slid tame finishes wide, while another effort from wide on the left did not trouble Dubravka.
Newcastle have another key home game next weekend as Bournemouth head to St James' Park, while Watford are on the road again, away at Southampton.