Substitutes Dentinho and Manor Solomon both scored second-half goals as Shakhtar stunned the 13-time European champions again, having already won 3-2 in Madrid in October.
Shakhtar had lost their last two Group B matches against Borussia Moenchengladbach by an aggregate score of 10-0, but this victory allowed them to move above Real into second place in the group with one game remaining.
Gladbach top the section, while Shakhtar now have the upper hand on Real thanks to their superior head-to-head record, while this result also means Inter Milan retain an outside chance of qualifying before their game later.
Madrid have made it out of their group in every year since 1997. If Gladbach beat Inter later, Real will no longer have their destiny in their own hands going into the final round next week.
Zinedine Zidane’s team were returning to the scene of their victory over Liverpool in the 2018 final, but they looked a shadow of their former selves in the snow in Kiev’s Olympic Stadium, and the result further underlined how much they miss defensive talisman Sergio Ramos when he is not there.
This was Real’s seventh defeat in the last nine Champions League matches they have played without Ramos, who is currently injured.
Perhaps this game would have turned out differently had Marco Asensio scored in the fifth minute rather than turn Karim Benzema’s cross onto the post, but they went on to slump to a third defeat in their last five matches in all competitions.
Dentinho had replaced the injured Junior Moraes in the first half and the Brazilian got the opening goal just before the hour mark.
Ferland Mendy intercepted a Viktor Kovalenko ball into the box but only succeeded in laying it on a plate for Dentinho to tuck past Thibaut Courtois and in.
The Ukrainian champions then made sure of their victory on the counter-attack with eight minutes remaining as Israeli international Solomon picked up the ball on halfway and advanced unchallenged before picking his spot.
