The players were taken from the field by referee Bjorn Kuipers towards the end of the second half, with a number of flares having been thrown onto the field.
Play subsequently resumed following a short delay, during which trouble appeared to break out in the area of the ground housing visiting fans, but neither side was able to find a winner.
Both teams came into Sunday's match, which had been threatened by heavy rain in Milan, boasting maximum points in Group H.
Italy took the lead through Antonio Candreva after 11 minutes when the Lazio man drove home from distance to beat Danijel Subasic as Croatia conceded for the first time in qualifying.
However, a rare Gianluigi Buffon error enabled Ivan Perisic to equalise within four minutes and Croatia created the better chances thereafter despite losing Luka Modric to injury later in the first half.
A game that saw both Daniele De Rossi and Ivica Olic win their 100th international caps had already been briefly halted following Perisic's goal as flares were thrown, and the various off-field incidents are likely to attract attention from UEFA.
Croatia were eager to test Buffon early on, with Ivan Rakitic letting fly from distance before Perisic and Modric both went close amid a flurry of early chances.
However, with one of Italy's first sights on goal, Candreva beat Subasic with a powerful strike from outside the area to put the hosts in front against the run of play.
Italy's lead proved short-lived as Perisic cut onto his right foot and fired low at Buffon, who failed to keep the effort out as it squirmed under his body.
A number of flares stopped play from resuming straight away, with fire officials required to put them out, but when it did Croatia were dealt a blow with the withdrawal of Modric shortly before the half-hour mark.
Italy were also forced into a switch as the injured Manuel Pasqual was replaced by debutant Roberto Soriano.
Such regular stoppages saw the game broken up, although Andrea Ranocchia was forced into a goalline clearance from an Olic header after Buffon capped a difficult half by flapping at a cross.
Home coach Antonio Conte turned to substitutes Stephan El Shaarawy and Graziano Pelle either side of Rakitic testing Buffon again shortly after the hour.
The Milan striker went close to finding the winner on his club's home ground when he fizzed a strike over Subasic's crossbar, before play was halted due to further crowd incidents, which intensified 20 minutes from time.
With smoke engulfing San Siro and ugly scenes in the stands, the players were brought off before eventually finishing the match.
Perisic then went closest to a winner - dragging a shot narrowly wide of Buffon's left-hand post following a Croatia break - with the draw ensuring the sides will sit level on 10 points going into 2015.
