Substitute Andy Carroll and captain Nicky Butt were denied by fine late saves from Plymouth goalkeeper Romain Larrieu as Newcastle had to settle for a draw at Home Park.
The Frenchman clutched Carroll's downward header from Ryan Taylor's cross and then tipped a deft lob from Toon midfielder Butt on to the crossbar to earn the Pilgrims a replay at St James' Park on Wednesday week.
Newcastle manager Chris Hughton had rotated his squad to the tune of seven changes, with only defenders Fabricio Coloccini and Danny Simpson plus Taylor and Alan Smith surviving from the side that had drawn 0-0 at home to Derby in their previous Championship match.
Taylor was moved into a back four into which Tamas Kadar was added while ahead of him, midfielders Fabrice Pancrate, Danny Guthrie and Butt and forwards Shola Ameobi and Nile Ranger were recalled. Dutchman Tim Krul replaced Steve Harper in goal.
The Pilgrims, currently under a transfer embargo, had no such luxury and were forced to give Chris Barker a seasonal debut at centre-back after just 60 minutes reserve-team match practice following a serious calf injury.
Barker replaced the Africa Cup of Nations-bound Reda Johnson.
It was Taylor who carved out the first opportunity of the game on a rutted, icy pitch after driving in a low cross from the right that picked out Pancrate on the near post.
The Frenchman's swinging foot totally missed the ball, however, and it rebounded off his shin to safety.
First-half chances were few and far between. Ameobi shot over the crossbar from long range while Argyle's Republic of Ireland international Alan Judge's volley at the other end met with a similar fate.
Ameobi did have the ball in the net after half an hour but referee Alan Wiley had previously blown for a foul by Pancrate on Gary Sawyer.
Just before the interval, Guthrie fired in a shot that man of the match Larrieu athletically turned aside, before Coloccini ended the half by firing wide after the Pilgrims defence failed to clear a free-kick.
The tight encounter continued after the break, with neither goalkeeper truly extended and opportunities to decide the tie at a premium until Larrieu's late heroics.