Athletic Bilbao held out with nine men to secure a first win over Barcelona in four years and carry a 2-1 lead into the second leg of their Copa del Rey last 16 tie on January 11.
Two goals in three first-half minutes from Aritz Aduriz and Inaki Williams put the hosts in command.
Lionel Messi's fine free-kick halved Barca's arrears after the break.
And the five-time World Player of the Year was inches away from a precious second away goal when he hit the post with the final kick of the game after Raul Garcia and Ander Iturraspe had been sent-off.
Enrique started all three of his star strike force of Messi, Luis Suarez and Neymar despite handing them an extended winter break which meant they only returned to training on Monday after two weeks off.
This is the sixth time Barca and Athletic have been paired together in the Cup in nine seasons, including three finals.
Barca have emerged victorious in all five previous occasions, but Athletic looked well on their way to reversing that run with two excellent goals midway through the first-half.
Firstly, Aduriz stooped unmarked to head home Garcia's cross and round off a fine team move on 25 minutes.
Then, in the midst of a homage to Athletic defender Yeray Alvarez who was recently diagnosed with testicular cancer, the hosts struck again when Williams smashed home a volley from Aduriz's neat backheeled layoff.
The match was then dogged by refereeing controversy as Aduriz escaped unpunished for an elbow on Samuel Umtiti.
Barca were even more incensed in first-half stoppage time when David Fernandez Borbalan somehow failed to point to the spot when Neymar was chopped down by Borja Etxeita.
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Barcelona players celebrates after scoring against Athletic Bilbao REUTERS
Andres Iniesta, Sergio Busquets and Jordi Alba were all booked for taking their protests too far, whilst Messi also had to be restrained from confronting Borbalan as the players left the field for half-time.
Borbalan did come to Barca's aid just after the break, though, when he adjudged Messi's free-kick to have crossed the line despite Gorka Iraizoz's best efforts in the Athletic goal.
More Messi magic nearly prevented Barca starting the year with defeat as he danced past two defenders before a desperate saving challenge from Mikel San Jose prevented the Argentine getting a shot off.
And in the dying seconds Messi smashed a loose ball inside the area off the inside of the post.