Hans Vanaken was the lucky recipient of McGregor's blunder as he was in the right place at the right time as the former Rangers stopper passed the ball straight to him, allowing the 32-year-old to round him and roll the ball into the net.
Defender James Chester came agonisingly close to making it 1-1 in the 89th minute but he missed the target with a free header from Sone Aluko's cross meaning the Belgian side will take the advantage into the return leg at the KC Stadium.
Only goalkeeper McGregor and Chester kept their places from Hull's Premier League opener against QPR at the weekend in a much-changed side.
Yannick Sagbo had the best chance of the first half for the visitors in the seventh minute and should have given Hull the lead, but he scuffed his shot allowing the Lokeren defence to clear.
McGregor was called into action at the other end to make a couple of saves and watched as Sergio Dutra Junior put a chance over the bar before Meyler fired wide from 20 yards as the first half ended deadlocked at 0-0.
There were no changes to either side at the start of the second period, with McGregor quickly brought into the action after saving a chance by midfielder Nill De Pauw.
The home side did take the lead soon after, though, when Vanaken scored from close range in the 58th minute after the Hull keeper was at fault.
McGregor took too much time on the ball and gifted possession to Vanaken, who rounded the Tigers' stopper and rolled the ball into an empty net.
Aluko tried his luck at the other end but dragged his low effort just wide of the post from about 25 yards out before Dutra again skied one over the bar on the turn.
In the 63rd minute, Lokeren defender Giorgos Galitsios chanced his arm with a long-range strike which drifted wide of the Hull goal before McGregor was called upon to make a crucial save to deny De Pauw.
Hull boss Steve Bruce responded with 20 minutes remaining by bringing on summer signing Tom Ince and striker Nikica Jelavic in a bid to get back on terms ahead of the return leg.
Sagbo and Brady made way and Ince came close to making an almost immediate impact when his goal-bound header was diverted behind by Verhulst with just over 10 minute remaining.
Ince had calls for a penalty waved away by the referee shortly afterwards and Chester went agonisingly close to making it 1-1 as the clock ticked down but he missed the target with a free header from Aluko's cross.
Hull were unable to find their cutting edge in the time that remained, meaning the Belgian side will take a one goal advantage to the second leg.
- Sports & Recreation
- Sone Aluko
- James Chester
- Hans Vanaken