Andre Breitenreiter guided Paderborn to promotion from the 2. Bundesliga in his debut campaign last season and the north-west club were on course to mark their maiden top-flight fixture with a win on Sunday.
Shinji Okazaki gave visitors Mainz a 33rd-minute lead by tapping home from close range after Paderborn keeper Lukas Kruse failed to hold on to a free-kick.
Paderborn's response was swift, though, and Elias Kachunga netted the club's first Bundesliga goal four minutes later with a fine finish from 20 yards.
The hosts thought they had won it in the 87th minute as captain Uwe Hunemeier nodded home, but the skipper went from hero to zero when he felled Okazaki in the box in injury-time.
The Japan international duly picked himself up to convert from 12 yards, giving new Mainz coach Kasper Hjulmand a point in his Bundesliga bow.
Sunday's other top-flight game also saw late drama as Borussia Monchengladbach salvaged a 1-1 draw in the 90th minute at home to Stuttgart.
Branimir Hrgota, who scored twice against Sarajevo in the UEFA Europa League in midweek, should have put the hosts ahead just after the break.
But the unmarked Swede inexplicably missed the target from close-range after latching on to an inviting cross from the right.
Stuttgart made the home side pay for that miss, as Alexandru Maxim lashed a half-volley under Yann Sommer after good work from Christian Gentner in the 51st minute.
Armin Veh's men could not hold on for the win, though, as Monchengladbach's World Cup winner Christoph Kramer fired in a late equaliser after getting on the end of Alvaro Dominguez's well-placed cut-back.
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