In the first-ever meeting between the two nations, USA went ahead after 30 minutes when Borussia Dortmund midfielder Reyna sent a deflected effort past Conor Hazard.
That was Reyna's second goal in four appearances for his country, with his strike making him the youngest player to score an away goal for USA (18 years and 135 days) since Pulisic against Saint Vincent and the Grenadines in September 2016 (17 years and 350 days).
Pulisic doubled the visitors' advantage in the 59th minute, stroking home from the penalty spot after he had been brought down inside the area by Daniel Ballard. That was the Chelsea man's eighth goal involvement in his last 10 appearances for his country (five goals, three assists).
Substitute Niall McGinn pulled one back for Northern Ireland in the 88th minute but it proved too little, too late for Ian Baraclough's side, who are winless in their last 12 matches across all competitions.