Thanks to some wasteful Rossoneri finishing, several last-ditch defensive efforts and first-half heroics from Nick Pope, Eddie Howe's men frustrated their hosts throughout the 90 minutes, coming away with a point despite not having a shot on target until the final seconds
A fit-again Sandro Tonali was brought back into the Magpies' XI for his San Siro homecoming, while Howe also made the bold decision to introduce Jacob Murphy into his attacking triumvirate.
Newcastle stifled Milan effectively in the opening stages, but they were soon subjected to a frenzied period of Rossoneri attacks, starting with Pope producing a fine double save to deny Tommaso Pobega and Samuel Chukwueze in the 13th minute.
Pope then had to be alert to thwart Olivier Giroud just three minutes later, before having to tip a Rade Krunic strike over the bar with 19 minutes on the clock, as Stefano Pioli's men suffocated their visitors.
Theo Hernandez was the next Milan player to be denied by the beleaguered Pope, who pushed his header over the top in the 21st minute, before Newcastle finally managed to relieve some of the pressure on their goal.
The visitors' respite was short-lived, though, as Rafael Leao skipped through a sea of black and white shirts inside the penalty area in the 34th minute before scuffing a backheel, and a follow-up from Pobega was cleared off the line by Murphy.
Howe's men improved following a much-needed half-time interval, albeit without testing Mike Maignan, and Pope was once again called upon to keep out Tijjani Reijnders's low strike in the 64th minute.
An injury to the effervescent Ruben Loftus-Cheek did not help matters for Pioli, while Tonali was also taken off not long after to a warm reception from the home crowd, who then witnessed Leao send a header a whisker over the bar from Alessandro Florenzi's cross in the 74th minute.
The hosts were dealt another bitter blow when first-choice goalkeeper Maignan - whose 2022-23 season was also disrupted by injury - had come off 10 minutes before the end, as Marco Sportiello came on for his debut in goal.
The Rossoneri shot-stopper was kept relatively quiet as Milan huffed and puffed for the opener, and Giroud saw his name up in lights in the 88th minute following a quick break, but with options either side of him, the Frenchman shot straight into the palms of Pope.
Five minutes of added time were signalled by the fourth official, the fifth of which saw Newcastle finally register a shot on target as Sportiello tipped Sean Longstaff's drive over the bar before also managing to deal with Kieran Trippier's last-gasp corner.
A Premier League clash with Sheffield United now awaits Newcastle before they host Paris Saint-Germain in two weeks time, while Milan are next in action against Hellas Verona on Saturday ahead of a trip to Borussia Dortmund on October 4.