Pulisic's 38th minute goal proved enough for the Americans to advance at the expense of their geopolitical rivals. Sergino Dest headed the ball into the path of the sprinting Pulisic, who swept it into the net to momentarily silence the raucous Iranian supporters in front of him but he crashed into the outstretched Alireza Beiranvand in the process.
Pulisic was back on his feet after receiving treatment for a few minutes but did not look comfortable and he was replaced by Brenden Aaronson at the break after sustaining an abdominal injury, in a major blow for the Americans' knockout stage hopes.
The U.S. finished two points behind Group B winners England to reach the last 16 for the fifth time since 1994. Iran finished third with three points, with Wales bottom with one point.
Gregg Berhalter's U.S. team, the second youngest at this year's finals, may lack experience on the big stage but they stepped up and delivered a commanding performance when their spot at the World Cup was on the line.