The 32-year-old Kruse returned to the Bundesliga this season after one year with Fenerbahce and needed only 13 minutes of his first start with Union to make his mark.
Sheraldo Becker was sent clear down the right and Kruse met his cross with a powerful header at the far post to break the deadlock.
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Kruse squandered another good chance in the 28th minute while Mainz, under interim coach Jan-Moritz Lichte following Achim Beierlorzer's sacking on Monday, failed to muster a shot on target in the first half.
Union increased their lead four minutes after the break with a simple goal after Christopher Trimmer got clear down the right and Marcus Ingvartsen slotted the ball in at the far post.
Trimmer also set up the third in the 63rd minute with another inviting cross which Marvin Friedrich headed in and substitute Pohjanpalo scored the fourth one minute later, 35 seconds after coming on for his debut.
It was the first time Union Berlin, who have four points from three games, had scored more than three goals in a Bundesliga match.
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