Defender Havard Nordtveit appeared set to be the unlikely hero as Hoffenheim - making its debut in the UEFA Champions League group stages - twice held the lead at the Metalist Stadium.
Florian Grillitsch gave Julian Nagelsmann's side an early advantage but his neat finish was cancelled out by Ismaily, who cut inside Nordtveit far too easily on Shakhtar's left before beating Oliver Baumann.
However, the former West Ham defender made amends at the other end of the pitch, flipping the script as he popped up at a corner to nod home what looked set to be the winner.
Shakhtar struggled to break open Hoffenheim in the second half until Maycon picked his spot from distance, firing a left-footed shot from outside the penalty area beyond goalkeeper Oliver Baumann.
The host came close to grabbing a late winner – Marlos seeing a goal-bound effort blocked by Taras Stepanenko, with Shakhtar's loud appeals for handball rejected – but the Bundesliga club just about held firm during a frenetic finish to pick up a point on the road.