Andrea Belotti gave Italy a 24th minute lead after the visitors, who have not lost in a qualifying competition for 10 years, had made a shaky start.
Ilija Nestorovski equalised in the 57th minute after Italy lost the ball in midfield and Feran Hasani struck again for the hosts two minutes later after another Italy mistake in midfield.
Macedonia were threatening to score a third when Immobile scored out of the blue in the 76th minute and he then headed the winner from close range in the second minute of stoppage time.
The win left Italy with seven points from three games in Group G, behind leaders Spain on goal difference.
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