Alexis Sanchez showed his class with a double to help Chile throw a spanner in the works of England's World Cup preparations with victory at Wembley.
The Barcelona forward nodded home after just seven minutes from Eugenio Mena's cross before a delightful stoppage time chip over Fraser Forster ended England's 10-match unbeaten run stretching back almost a year.
Goalkeeper Claudio Bravo saved well from Phil Jones and Frank Lampard in the first half but Roy Hodgson's men created little of note after the break and on Tuesday face Germany - among the favourites in Brazil next summer - off the back of their first home defeat since February 2012.
With the aim of impressing Hodgson ahead of selection for next summer's World Cup finals, Fraser Forster, Adam Lallana and Jay Rodriguez were all handed debuts in three of eight changes for an injury hit England from the win over Poland which secured qualification for Brazil.
Only Argentina and Colombia finished above Chile in South American qualifying for the World Cup and with Jorge Sampaoli's side protecting a nine-match unbeaten run Hodgson's experimental England team couldn't take their opponents lightly, particularly with the visitors having Sanchez to call upon as well as Cardiff City midfielder Gary Medel.
But despite being much changed, England began on top with Jones forcing Bravo into an acrobatic save before Lallana's cross-caused problems with the Chile skipper again having to be alert.
Despite the encouraging opening it took little time for Chile to find their stride and after a slick passing move which first saw Gary Cahill block Charle Aranguiz's goalbound effort, Eugenio Mena crossed for Sanchez, who got ahead of Leighton Baines and stooped to direct a low header into the corner leaving Forster helpless.
Chile's high pressing game was causing England problems as they built from the back and Forster prevented the lead from doubling as he produced a smart stop from Jean Beausejour after Sanchez fed the Wigan Athletic man.
Having scored 29 goals but conceded 25 in qualifying for the World Cup, Chile's attacking threat was always likely to be tempered by defensive inadequacy and the chances did continue to come for England, albeit from range.
Lampard, on the evening where his achievement of reaching a century of international caps was marked with the captain's armband and the presentation of a golden cap, saw a 35-yard free-kick tipped over by Bravo, James Milner's effort was deflected onto the roof of the net by Medel and Jack Wilshere's drive was beaten out by the Chile stopper.
The underlining Chile threat remained however and Forster again had to be alert after Fernandez moved the ball on to Beausajour, but the wide man failed to control when well placed in the right-hand channel of the penalty area.
And England should have capitalised by levelling on the stroke of the break when Wayne Rooney found Lallana, but the Saints forward dragged his effort wide.
After seeing little improvement from an unchanged England after half time, Hodgson introduced Andros Townsend and Chris Smalling prior to the hour mark but it brought little change for the hosts.
While England had seemingly nullified the Chile threat, with their defensive line dropping as the half wore on, they were finding chances hard to come by at the other end with periods of sustained possession few and far between, despite the introduction of Jordan Henderson and Tom Cleverley.
Such idleness in possession allowed the visitors to crown victory with a well taken second as Smalling was caught, with Sanchez going through before drawing Forster as Chile layed down a marker down ahead of next summer and provided food for thought for Hodgson ahead of Tuesday's friendly against Germany.