Arkadiusz Milik's 51st minute strike ensured Poland claimed a 1-0 win in Nice after dominating the contest.
Northern Ireland, which boasted the longest unbeaten run of any team at Euro 2012, rarely looked like finding a way back into the contest after Milik's strike.
Poland, boasting a strike force of Milik and Bayern Munich's Robert Lewandowski, created a number of chances but struggled to find a way past a determined Northern Irish defense.
Bartosz Kapustka, who impressed throughout the game, went close in the first half with a fine curling effort which was well saved by Michael McGovern.
Poland, which had failed to win any of its six previous games in European Championship history, began to grow frustrated with its inability to convert possession into chances.
Northern Ireland, playing at the tournament for the first time, looked comfortable at the interval despite failing to register as an attacking force.
But its defense was breached six minutes after the restart when Milik danced his way into the penalty area and fired the ball into the corner.
Northern Ireland, which had sat deep and absorbed pressure for so long, attempted to throw off the shackles but struggled to create anything of note.
Conor Washington, a second-half substitute, was denied by Wojciech Szczesny in the Polish goal, while Steven Davis was inches away from connecting with a pass at the far post.
Poland, growing visibly nervous, began to drop deeper and deeper as the game entered the final minutes.
But Northern Ireland was unable to find an equalizer as its return to the big stage ended in a first defeat in 13 games.