A late Joe Allen goal and a string of superb saves from Stoke stopper Lee Grant earned the struggling visitors a point and deny dominant United victory.
33-year-old Derby loanee Grant, deputising for long-term injury victim Jack Butland, produced a man of the match showing to continually deny the profligate hosts with a series of top class stops that left Jose Mourinho's side frustrated.
Substitute Anthony Martial curled home an excellent finish for his first of the season to finally put United ahead but former Liverpool man Allen equalised from close range on 82 minutes to give Mark Hughes side a first ever Premier League point at Old Trafford.
The Reds started brightly and could have gone in front inside two minutes when Paul Pogba's exquisite pass picked out Zlatan Ibrahimovic but Grant reacted well to keep out the Swede on the angle.
Geoff Cameron twice went close for the visitors as Stoke settled into the game, but United continued on the front foot and should have been out of sight by the break.
Pogba twice went close when he fired narrowly off target after excellent build up play between Ander Herrera and Zlatan, before the Frenchman headed wide of the post from a Daley Blind corner when well placed.
Grant saved brilliantly from Jesse Lingard's snap-shot and had to be at his best again soon afterwards to tip Juan Mata's lovely lob over the crossbar shortly before another effort from Ibrahimovic was clawed behind by the sprawling keeper.
Allen side footed straight at De Gea who tipped over a Bruno Martins Indi effort from distance- although the offside flag was up- while opposite number Grant continued to enjoy the finest day of his journeyman career to date.
He saved from Mata from range and also reacted well to keep out the impressive Pogba while Ander Herrera thumped inches wide with a 25 yarder after Lingard had cut the ball back.
A low strike from Ibra drifted narrowly off target before United suddenly came to life and finally broke through through Martial moments after his introduction.
It was a goal reminiscent of his sublime effort in last year's corresponding fixture when he finished excellently from 12 yards after intricate link up play with Mata.
Stoke should have been dead and buried but Grant continued to come to their rescue as he beat away an Ibrahimovic volley and then tipped wide from Herrera's header.
United were made to rue the keeper's heroics as Stoke found themselves level with eight minutes to play when David de Gea failed to hold Glen Johnson's shot, Jon Walters follow-up came off the woodwork and Allen poked in from close range.
United lay siege to the Stoke goal as Pogba headed against the bar late on but no last gasp winner was forthcoming on a frustrating afternoon for the Reds.
Overall team performance: 8/10
United Faithful Man of the Match: Juan Mata