Former Hamburg youth player Rouwen Hennings gave the second division side the lead, but an Ivo Ilicevic strike 17 minutes from time brought the hosts back level in the tie, which will be completed at the Wildparkstadion on Monday.
Hamburg will have to score there to stand any chance of maintaining their 52-year top-flight status with the away-goals rule applied if the two sides are still level at the end of 90 minutes in the second leg.
Hamburg benefited from the away-goals rule to see off Greuther Furth in the play-off a year ago and here they were again, needing two extra games to secure their top-flight status.
Their hero last season was Pierre-Michel Lasogga and he recovered from a shoulder injury to take his place in Bruno Labbadia’s attack on Thursday.
The early action was at the other end of the field, though, with Karlsruher taking a fourth-minute lead through Hennings, a product of the Hamburg youth academy.
Dimitri Nazarov’s pass wide to Hennings was arrowed into the far corner of Rene Adler’s goal to silence the Volkspark Stadion.
No Bundesliga side has ever recovered from losing the first leg to survive relegation and this may have been in the Karlsruher players’ minds as they started to close off all the avenues towards their goal and preserve their lead.
For all of their possession, Hamburg were unable to craft a way through, meaning the visitors were good value for their lead at the interval.
Karlsruher could have doubled their advantage early in the second half, but after Manuel Torres struck the crossbar, Nazarov followed suit with a stunning effort from distance.
Both efforts rattled the frame of the Hamburg goal, and they also rattled Labbadia’s men, who built up a head of steam in the search for an equaliser.
Ilicevic exchanged passes with Dennis Diekmeier to find a way through finally and pick his spot low into the far corner.
Hamburg peppered Dirk Orlishausen’s goal in search of a winner, but it was not to be, meaning the two sides will reconvene on Monday to determine who will be the 18th side in the Bundesliga next season.