Goals in each half from Marie Detruyer and Elisa Polli were enough to send the Italian side away victorious.
United were put under pressure in the opening 45 minutes and could have been more than 1-0 down; however, the second half was all Newcastle, and they created plenty of chances to take positives moving forward.
Inter Milan gave United some early warning signs when Elisa Bartoli nipped in at the back post to tap home past Kayla Rendell, only for the officials' flag to keep the scores level.
Newcastle showed the visitors they could pose their own threat with a swift counter-attack from Kathleen McGovern who broke from her own half before feeding Beth Lumsden on the right, but after cutting onto her left foot her shot was easily saved.
However, Inter Milan got themselves in the lead after 26 minutes when a low cross from the right missed everyone in lilac, but Detruyer pounced at the back post to finish beyond Rendell.
The Lasses almost found themselves going into the break 2-0 down after Detruyer disposed Hildur Antonsdottir before picking out Benedetta Gilonna who only had Rendel to beat, but her curling effort was well wide of the far post.
Newcastle came out firing in the second half and should have levelled things up through McGovern, who found herself unmarked in the six-yard box, but despite Jordan Nobbs finding her, she was denied by a stunning save from point blank range.
As the game ticked over past the hour mark, substitute Jessie Gale found herself bearing down on goal with her first touch of the game, but as she looked to round Runartsdottir, the Icelandic keeper got down well to stop her advances.
While United were certainly under pressure in the first half, it was all Newcastle in the second half.
McGovern was afforded another chance to score her first goal for the club when Leanne Kiernan picked her out unmarked with a lofted ball, but her half volley was tame and easily gathered by Inter Milan’s goalkeeper.
Despite creating several chances throughout the second half, it was Inter who struck the killer blow. A long ball over the top saw Benedetta Glionna race in behind and calmly cut the ball back for Elisa Polli, who calmly curled her effort beyond Anna Tamminen.
Newcastle United Women: Kayla Rendell (Anna Tamminen 46), Jemma Purfield (c) (Gemma Evans 46), Kathleen McGovern (Martha Thomas 77), Mollie Lambert (Jordan Nobbs 46), Emilia Larsson (Jessie Gale 60), Hanna Nemeth (Aoife Mannion 46), Hildur Antonsdottir (Ashanti Akpan 77), Kaitlyn Torpey (Freya Gregory 67), Lois Joel (Katie Bradley 60), Beth Lumsden (Leanne Kiernan 60), Rachel McLauchlan (Charlotte Wardlaw 67)
Subs not used: Demi Stokes, Oona Sevenius, Casi Gregson, Abbie Richardson
