Western Sydney could essentially bow out of the AFC Champions League as early as Tuesday night since this loss leaves their knockout-stage chances out of their hands.
Terry Antonis and Lachlan Scott scored late goals to give the Wanderers a glimmer of hope on Tuesday night but the cavalry came too late as they suffered their third loss in four games to slip to the bottom of Group F with three points.
The 2014 ACL champion Wanderers are all but out of the running for the knockout stage after Urawa Red Diamonds defeated Shanghai SIPG in the group's other game, to move to the top of the standings, on nine points, by virtue of a better head-to-head record against the Chinese side.
Having previously lost by four-goal margins to Urawa and Shanghai, the Wanderers would need results to go their way and overturn the head-to-head deficit to progress as one of the top two teams in the group.
On a three-day turnaround after Saturday's A-League draw with Melbourne Victory, Western Sydney dominated possession but struggled to penetrate without benched stars Nico Martinez and Brendon Santalab.
Four minutes in they were already on the back foot when Lee Seok-hyun emerged from nowhere to blast home from 25 metres.
Seoul were assisted in the first half by the Wanderers, who were their own worst enemy at times.
Jumpei Kusukami bore in on goal and should have shot when one-one-one with the keeper but inexplicably opted to cut back for Mitch Nichols to sky his subsequent finish.
Scott Neville was left with a bleeding head after being taken out by teammate Aritz Borda in an aerial contest at a corner.
Neville was replaced by Brendan Hamill at half-time but played on long enough to concede a penalty for a relatively soft push on Brazilian attacker Maurinho.
Veteran Montenegrin striker Dejan Damjanovic converted from the spot on 42 minutes.
Seoul increased their lead in the second half with Demjanovic capitalising on some loose marking to clinically find the net from the edge of the box.
Just as the contest appeared over, Jumpei came good in the 77th minute with a neat pass to set up Antonis's goal before substitute Martinez crossed for Scott to score in injury-time.