The English side kicked off their attempt with defeat against Sporting Lisbon, while the Blaugrana's famous academy side rescued a point and CSKA Moscow beat Molde
Michael Drennan fired the English side’s youngsters into the lead, but the Portuguese side levelled through Ecklino Le, before Carlos Mane and Tobias Figueiredo's spot kick ensured all three points for the visitors.
The Lisbon-based club are strongly-fancied for the competition, after having produced the likes of Cristiano Ronaldo, Nani and Luis Figo from their academy over the years.
Barcelona's famous academy, meanwhile, survived a scare after falling behind to Belgian outfit Anderlecht courtesy of Nathan Kabasele's 66th-minute strike.
But the Blaugrana's blushes were spared when Toni Sanabria salvaged a point late on.
In the evening's other fixture, CSKA Moscow began their NextGen campaign with a home victory against Norwegian club Molde, courtesy of Dmitry Litvinov's 74th-minute winner.
"We are delighted to get this season underway, and tonight has been a brilliant start," said Justin Andrews, co-founder of the NextGen Series.
"The games have been very high in quality and they have set a benchmark of what we can expect to see throughout the coming weeks and months in the competition."