Latics almost repeated the heroics of last week as they came back from 2-0 down to draw level, but they were ultimately disappointed as Port Vale grabbed the winner in stoppage time.
Vale went ahead through Anthony Grant on 33 minutes and then doubled their lead on 63 minutes through Louis Dodds, but Latics then staged a late comeback with goals from Chris McCann and Leon Barnett.
But as Latics pressed for the winner they were caught out in defence as Barnett received a straight red card on 88 minutes for a foul on Enock Andoh. With Latics reduced to ten men the Valiants produced a dramatic soul-destroying last-minute winner through Uche Ikpeazu.
Gary Caldwell made two changes from the victory at Chesterfield. Sean Murray was replaced by McCann in midfield while Max Power was replaced by Jonjoe Kenny who was returning from international duty with England U19s.
After an even opening the best chance fell to McCann on 30 minutes after a low cross from Craig Davies, but the Irish midfielder was unable to apply the killer touch.
Somewhat bizarrely referee Mark Haywood then allowed the players a drinks break, and as at Gillingham, the home team scored from the restart as Latics switched off.
Carl Dickinson crossed from the left and McCann looked to have cleared the danger but he only played the ball into the path of Anthony Grant, who produced an unstoppable drive past Richard O’Donnell into the Latics goal.
Just before the interval Caldwell made a double substitution with Jody Hiwula and Andy Kellett replacing Haris Vuckic and Donervon Daniels.
Latics were put under pressure at the beginning of the second half and it looked only a matter of time before Vale would increase their lead.
Vale did double their lead from a corner in the 65th minute after some inept Latics defending, Louis Dodds smashing the ball into the net from close range.
Almost immediately Latics replaced Reece James with Will Grigg and the Irish striker had an instant impact. Davies got behind the Vale defence down the right hand side and pulled the ball back to McCann who side footed the ball past Alnwick and into the Vale net.
The prospects of another Wigan comeback were now on the cards and the 1,300 fans behind the goal began to sing ‘We’re going to win 3-2′.
Latics were now pressing for the equaliser with Davies at the centre of their best moves. The big striker almost got on the score sheet but Alnwick was able to save at the second attempt. Davies then fired another great effort across the face of goal before McCann fired his effort straight at Alnwick. Grigg then went down under a challenge from Richard Duffy but referee Haywood waved away Latics’ appeals.
Vale responded and O’Donnell had to produce an outstanding full length save to deny Dodds. It was end-to-end stuff now with both teams creating chances, but it was Latics who drew level on 83 minutes.
Michael Jacobs’ well flighted corner was met by Barnett who rose on the six yard box to head the ball powerfully past Alnwick.
Latics fans were jubilant and sensing another amazing comeback. But the game turned back in Port Vale’s favour on 87 minutes.
As Wigan pressed for the winner they were caught on the break and last man Barnett committed a professional foul on Enoch Andoh and was issued with a red card.
As the match moved into stoppage time Latics were unable to repel yet another Vale attack and the ball fell to Uche Ikpeazu who finished from close range to send the travelling army home disappointed.