The visitors made the perfect start, dramatically after only three minutes.
A defensive error from Venezia defender Seid Korać gifted Reid a golden opportunity to give the Green and White Army the lead, but his close-range effort was well saved by Anthony Moris.
However, the referee was soon called over to his video monitor to review footage of a possible handball by Korać during the incident, eventually awarding a penalty.
Isaac Price stepped up to take the spot-kick but saw his effort palmed away by Moris.
The quickest player to react was Reid, who slammed the rebound into the back of the net to put Northern Ireland ahead early on with his second senior international goal.
The volume inside the Stade de Luxembourg was turned up to 11 when striker Aiman Dardari levelled things up at the half-hour mark.
After receiving a pass from Danel Sinani, Dardari waltzed along the edge of the 18-yard box before firing the ball out of Bailey Peacock-Farrell’s reach and into the bottom corner for his first-ever goal for the Red Lions at senior level.
However, the home crowd were almost muted on the stroke of HT when Devenny’s excellent free-kick crashed off the woodwork from 20 yards out.
O’Neill’s HT team talk was clearly an inspired one as it took Northern Ireland just 22 seconds after the interval to restore their lead when Charles’ deflected effort from outside the box wrong-footed Moris and smashed the back of the net.
Things turned from bad to worse for Jeff Strasser’s side when Korać was shown a second yellow card just before the midway point of the second period.
It took only four minutes for the visitors to take full advantage of the extra man. A long delivery into the penalty box was not dealt with properly by the Luxembourg defence, which allowed Devenny to rifle the ball home and extend Northern Ireland’s lead.
After this, there was no way back for the hosts, and the Green and White Army cantered to victory.
Northern Ireland haven’t featured in a WC since 1986 when the likes of Gerry Armstrong and Pat Jennings played for their national team.
Thursday night’s victory over Luxembourg will surely have Norn Iron fans dreaming that this is their time to shine and return to the biggest stage of them all.
For Luxembourg, new manager Strasser will have plenty to ponder following a disappointing home defeat in his first game in charge.
Flashscore Man of the Match: Shea Charles (Northern Ireland)
