Leighton Baines started for England against Chile at Wembley but was caught out at the far post when he allowed Alexis Sanchez to get ahead of him and nod the visitors in front.
It was a below-par display from the full-back, who also struggled to get forward and link-up with debutant James Rodriquez.
Teenager Ross Barkley came off the bench in the 77th minute to win his second cap but couldn't swing the game back in England's favour. An error by Gary Cahill allowed Sanchez to claim his second in stoppage time and seal the win.
Phil Jagielka didn't make it onto the pitch but is expected to start for the Three Lions in the showpiece friendly against the old enemy Germany at Wembley on Tuesday.
North of the border things fared better for goalkeeper Tim Howard. Howard captained the USA in the match with Scotland in the absence of the injured Clint Dempsey and put in an assured display, making a fine stop from a Robert Snodgrass free-kick to secure a goalless draw. Forward Steven Naismith also made an appearance as a 81st minute substitute.
Across the Irish sea Seamus Coleman and James McCarthy started for the Republic of Ireland against Latvia in what was Martin O'Neill's first game in charge.
Coleman played the whole game and set up the final goal for Shane Long in the 3-0 victory. McCarthy played 81minutes before being replaced by Kevin Doyle. John Heitinga didn't feature for Holland as they drew 2-2 with Japan in Belgium on Saturday evening.
On Thursday Romelu Lukaku and Kevin Mirallas featured for Belgium, Gerard Deulofeu shone for Spain Under-21s while Nikica Jelavic saw Croatia's draw with Iceland from the bench.
Roberto Martinez will be relieved that his players came through the first set of international fixtures unscathed - the memory of Darron Gibson's season-ending knee injury playing for Ireland last month is still fresh.
However, with another set of games to come on Tuesday it is still too soon to assess the fitness of the squad ahead of next weekend's looming Merseyside derby.