Croatia went into the encounter knowing a win over Italy would guarantee them a last-eight place, but they were decidedly second best in the opening 45 minutes at Poznan's Municipal Stadium.
Italy deservedly led at the half-time interval courtesy of Andrea Pirlo's stunning free-kick, but were never the same attacking force in the second period, allowing Mandzukic to equalise in the 72nd minute.
With four points from two matches, Croatia now face a challenging final clash with reigning world and European champions Spain.
As for Italy, who have now drawn both of their matches, they know they will have to beat the Republic of Ireland on Monday to be in with a chance of a quarter-final spot.
Although Italy coach Cesare Prandelli remains unbeaten in competitive internationals with eight wins and four draws, he will likely feel this was a game that should have been won in the first half.
Italy signalled their intent inside three minutes, via Manchester City striker Mario Balotelli in particular.
Receiving Emanuele Giaccherini's left-wing ball inside the area and with his back to goal, Balotelli made one touch and a sharp turn before firing a 12-yard left-foot shot narrowly wide.
It was the start of a predominantly one-sided half, with Claudio Marchisio shaving the crossbar with a rasping 20-yard drive just eight minutes later.
A further opportunity for Balotelli, with a snap shot straight at goalkeeper Stipe Pletikosa, and an Antonio Cassano flick through the six-yard box sandwiched Croatia's one significant chance.
That came in the 20th minute when Darijo Srna played a piercing low ball from the right into the near post.
All that was required was the merest of touches from Nikica Jelavic that would potentially have been enough to beat Gianluigi Buffon, but instead the veteran was allowed to collect.
Italy, though, retained their stranglehold on the game and should have taken the lead eight minutes from the break, only for Marchisio to twice be denied by Pletikosa.
After a delightful touch to leave Srna for dead inside the area following a through ball from Cassano, Marchisio's initial left-foot shot was superbly saved by Pletikosa, who then blocked the follow-up at point-blank range.
But with the danger still present, Ivan Ratikic fouled Balotelli on the edge of the area, allowing Pirlo to whip a 21-yard right-foot free-kick over the wall and inside Pletikosa's right-hand post.
It left Slaven Bilic's side going into the break knowing they had to up the tempo and chase the game in the second half, which they at least started with greater urgency.
But after Luka Modric first fired a 20-yard shot a yard over the bar the encounter turned scrappy, dominated by niggly fouls and challenges until Balotelli came within inches with a fierce drive on the hour.
Then finally, in the 72nd minute, Croatia made their presence felt in the right way as their two-goal hero from the 3-1 win over the Republic of Ireland struck again.
Ivan Strinic's ball from deep on the left wing was missed by Giorgio Chiellini, allowing Mandzukic to control and beat the advancing Buffon in off the right-hand post from six yards.
Croatia finished the game the stronger as they went in search of the winner that would have sealed their last-eight place, but it was not to be, leaving both sides facing a dramatic final group game.