Michael O'Neill's visitors held their own for 80 minutes but saw their brave resistance broken by substitutes Eduardo Vargas and Mauricio Pinilla.
Both men had started on the bench, along with Barcelona star Alexis Sanchez, but all three were needed to stop the party atmosphere falling flat.
As with Northern Ireland's 1-0 defeat in Uruguay last week, it was a performance O'Neill could take heart from - not least after a pair of first-half free-kicks that might have given his side the lead.
But it was still another loss and a fourth successive outing without scoring.
As it was, Northern Ireland almost ended their drought in the opening seconds, when the ball fell kindly for Billy McKay.
The Inverness striker managed a clean connection from 25 yards but Johnny Herrera was well placed to make the save.
That aside, Chile dictated the pace and looked to starve their opponents of possession.
For Northern Ireland, only Steven Davis' tireless running kept his side's heads above water, with the captain covering every inch of grass and stifling a handful of attacks with timely challenges.
Aaron Hughes was leading the back-line well too, with Chile's selection of flicks and tricks yielding nothing better than a free-kick harshly given against goalkeeper Roy Carroll for handling outside the area.
Indeed, it was Northern Ireland who went closest to breaking the first-half deadlock from a pair of free-kicks won by the industry of Ryan McLaughlin - starting for the first time - on the right wing.
Brother Conor McLaughlin's 20th-minute header, from Shane Ferguson's tempting delivery, was destined for the net had Herrera not made a smart save.
Oliver Norwood went direct in the 38th minute, whipping a shot to the near post where Herrera again scrambled the ball to safety.
In the first half I thought we were excellent but in the second half it was a case of fatigue. We're a month out of our season going against a team heading to the World Cup.
NI manager Michael O'Neill
For all their territorial superiority, Fabian Orellana's scuffed effort was the best Chile could do in response.
As the hour mark approached, Jorge Valdivia saw what appeared to be a cross veer towards the top corner and thought he had scored until Carroll backtracked and clawed to safety.
Moments later, Sanchez made his belated arrival and was almost gifted a bizarre winner when Conor McLaughlin's clearance cannoned off him and needed a sprawling save from the alert Carroll.
Valdivia should have scored moments earlier but headed against the post after Gary Medel's flick left him with a six-yard finish.
The strength of Chile's bench eventually told, Sanchez's chipped through-ball teeing up Vargas for the headed opener 10 minutes from time.
He appeared to be marginally offside, but the result was sealed with a second when Pinilla raced into space before depositing a clinical low strike across Carroll.
Meanwhile, Northern Ireland manager Michael O'Neill has declared his side's South American tour a big success despite them slipping to a second defeat.
O'Neill was primarily focused on the chance to work with his side for an extended period and building team spirit.
"I've got a huge amount more than I anticipated from the trip," O'Neill said after watching late goals from Eduardo Vargas and Mauricio Pinilla end any hopes of a battling draw.
"I'd have to say, in all honesty, it's been the best 10 days I've had in the job and I've just told the players that.
"They've been a joy to work with and in terms of their application, even the lads who didn't get the chance. It's been a really positive atmosphere.
"Steven Davis and Aaron Hughes have both said it's as good a trip as they've been on and given they've got 150 caps between them that is testament to it.
"The bonding that has gone on has been really good, with the younger players bringing that freshness and the older players responding to that."