Chasing a modest 190 to win, Nepal, playing their first 50-over game since securing ODI status earlier this year, were bowled out for 134 with more than eight overs to spare.
Nepal had got off to a flying start in their run chase.
They looked comfortable at 85-1 before they slipped quickly to 104-6 and with most of their stroke makers back in the pavilion.
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Opening batsman Gyanendra Malla hit 51 off 61 balls with eight fours and enjoyed a first-wicket stand of 58 with teenage wicketkeeper Anil Sah (21).
But once skipper Paras Khadka became the second wicket to fall and Malla was then dismissed by South African-born all-rounder Michael Rippon, Nepal's challenge petered out.
Dipendra Singh Airee (33) was the only other Nepalese batsman to reach double figures.
For the Dutch, playing their first ODI in four years after losing their one-day status, seamer Fred Klaassen took 3-30, leg-spinner Rippon finished with 3-23 while orthodox slow bowler and skipper Pieter Seelaar claimed a miserly 3-16.
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Earlier, Rippon had top-scored for the Dutch with 51 while Khadka claimed the best bowling for Nepal, leading from the front with 4-26.
Sompal Kami took 3-34.
The second and final match of the series will be staged at the same venue on Friday.
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