After Sunday's humiliation on the same pitch, FC Nordsjaelland coach Jens Fonsskov Olsen had reshuffled his tactical lineup and dictated a 5-3-2 formation.
Contrary to tradition, the visitors allowed FC Midtjylland to dominate possession to bolster their defense. It worked well for about 30 minutes, but then the FC Nordsjaelland rearguard collapsed completely.
In the 34th minute, Junior Brumado poked the ball over the line from close range, and six minutes and 57 seconds later, the home side had scored two goals further to put themselves in solid control of the match.
FCN's defense could not withstand the pressure from FC Midtjylland, especially on set pieces and crosses into the box. Brumado scored his second of the night to double the lead, while his attacking colleague Gue-Sung Cho produced a bullet header to make it 3-0.
The visitors also had a nightmare start to the second half when Brumado completed his hat trick to make it 4-0 by converting a penalty five minutes after the interval.
Peter Ankersen gave the visitors a very small lifeline when he curled the ball home from the edge of the box with ten minutes to go. But the FC Nordsjaelland celebrations were cut short as Mikel Gogorza just a minute later restored the four-goal advantage to leave the visitors with a mountain to climb in the return leg.