The last ball from Ben Clements saw a run out attempting a third run which would have levelled the scores as Cricket Wales closed on 128-9.
Worcestershire won the toss and opener Louis Hursthouse struck 46 off 38 balls.
Fin Goodman made a useful 23 and there were late order runs from Henry Hawes (19 not out) and Toby Cox (16 not out) in a total of 129-5.
When Cricket Wales replied, Ben Clements removed both openers cheaply and Cox had 3-23 from four overs as Worcestershire won by the narrowest of margins.
They had been edged out by the same opponents earlier in the day in a ECB T20 Group Two encounter.
Seth Essenhigh gave Worcestershire early momentum by making 44 off just 19 balls with four sixes and two fours.
Lucas Ingram and Hawes (both 18 not out) and Joshua Leach (17) were the other main contributors to a total of 129 all out.
Cricket Wales were reduced to 1-2 but Sami Khan (59) was largely responsible for his side winning by three wickets with one ball to spare.
Ben Clarke (4-0-14-2), Leach (4-0-27-1), Hawes (2-0-21-1) and Clements (2.5-0-25-1) were the Worcestershire wicket-takers.
