United have won just one Premier League game since mid-September and were outfought and outclassed by Watford at times at Vicarage Road.
Goals from Joshua King and Ismaila Sarr had the hosts two up at the break, only for Donny van de Beek to pull one back for the visitors. But a miserable afternoon was made worse for Solskjaer when Harry Maguire was dismissed, before Joao Pedro and Emmanuel Dennis added to the pain in stoppage time.
The loss leaves United outside the European spots and five points off fourth-placed Liverpool, who play Arsenal later on Saturday evening.
It comes after the final international break of the year had seemingly given Solskjaer breathing space to correct issues within his squad that were badly exposed in the placid 2-0 defeat to Manchester City at the start of the month.
Solskjaer went with a forward line of Marcus Rashford, Bruno Fernandes and Jadon Sancho behind lone forward Ronaldo. In midfield, Nemanja Matic was favoured over Fred to partner Scott McTominay.
But once again United looked frail. King had time and space to side foot home in the box midway through the first half, while Sarr lashed in a drive before half time after neat work from Kiko Femenia down the right.
Even before going down to 10 men United were lacklustre in possession. Van de Beek’s tap-in from a Ronaldo knock-down was a brief flash of brilliance in an otherwise passive afternoon for the visitors.
As for Maguire, his rollercoaster season at United took another turn. The England centre-back was first booked for a lunge on Sarr after being turned by the forward. And he was sent off seven minutes later when hacking Tom Cleverley down after losing the ball to the former United man.
Pedro and Dennis inflicted further pain at the death to send the United supporters trudging towards the exit.
Solskjaer looked on in dismay, impotent on the sidelines. Having suffered a seventh defeat in 13 games, he might be heading to his own exit door.