Having made a whole host of changes to allow various squad members playing time, Vale lacked the batting depth to enable them to overhaul their target.
Faced with Highgate's total of 188, LMV limped to 147 as they struggled against the accuracy of the home side's bowlers on a tricky, slow wicket.
Vale would have been happy enough at the break after restricting Highgate to below 200.
David Marks (3-39) rolled back the years to mark his return to the fold, whilst Neil Lederman (3-10), bowling for the first time this season following shoulder problems, took control in the middle overs and will hope to feature more prominently as the season progresses.
Sam Wolfson (1-14) also made a notable contribution, picking up his maiden wicket for the club in an impressive spell.
In response, Danny Caro and Sam Clarfield looked in fine fettle - but after laying the foundations for Vale's chase, they fell in quick succession and Vale were on the back foot.
Steven Allweis took his time to steady the ship and top-scored for LMV with 29, but despite useful knows from Lederman (19), Rafi Saville (20) and Jonti Aremband (15), there was too much to do for the lower order, and Vale fell short of their required target.
It is back to league action next week for the team, with the visit of Brondesbury to Rowley Lane.