The Magpies' second-string will be based in Pinatar for a warm weather training camp before Elliott Dickman's side take on Elche at the 3,500-capacity Pinatar Arena on Saturday, 16th July (kick-off 7pm local time).
United's under-18 side will also be travelling with the under-21 group as they continue their preparations ahead of the 2022/23 season, with the Toon teenagers set for a friendly clash against Selección Region de Murcia at the same venue (kick-off 11am local time).
Academy Director Steve Harper told nufc.co.uk: "The trip to Pinatar provides an excellent opportunity to get both new professional development phase (PDP) groups (U18 and U21) working closely together in a warm weather training camp.
"We are very grateful for the support of the owners in allowing both groups to travel to Pinatar and during their stay, everyone will be working hard at fantastic facilities supported by an extensive, excellent support team.
"Both groups will finish with a fixture at the end of the week and for the new under-21 group to have a very tough test against a very, good La Liga side in Elche shows what opportunities being a young player at Newcastle United can provide."
Summer signings Alex Murphy and Charlie McArthur, who joined the Magpies' youth set-up from Galway United and Kilmarnock respectively, will be on the flight to Spain along with the likes of Joe White, Jay Turner-Cooke and Isaac Westendorf, who have all trained with Newcastle's first-team in recent weeks.
Supporters can go behind-the-scenes of Newcastle United Under-21s' visit to Spain with content across nufc.co.uk and the club's official social media channels.
