Captain William Porterfield hit a stunning 127 not out, the first T20 international century for Ireland, to lead his side to 216 for three and the USA could only respond with 141.
Porterfield reached his half-century from 23 balls and put on 94 in eight overs with opening partner Paul Stirling before the latter was bowled by Karan Ganesh for 25 from 17 balls.
Kevin O'Brien made 18 and Trent Johnston seven but Ireland were 151 for two with four and a half overs remaining when Porterfield, on 94, was joined by John Mooney.
Nineteen runs came from the 17th over, Mooney with two sixes and a four, and Porterfield reached three figures in the 18th over, from 60 balls.
He then hit a six and two fours off successive Srini Santhanam deliveries and two fours in the last over from rival skipper Neil McGarrell, and h is 69-ball onslaught featured 12 fours and five maximums. Rooney finished 32no from 13 balls in a 27-ball stand of 65.
The Americans started well in their run chase as Akeem Dodson (27), Timroy Allen (20) and Steven Taylor (17) saw them to 57 for one in six overs.
But spinners Stirling (three for 25) and George Dockrell (two for 19) put the brakes on the chase and despite McGarrell's 23, the result was never in doubt.
Ireland, who face Italy on Thursday, are ahead of Hong Kong on net run rate and have played a game less but still have to face their closest pursuers.