The United States are unbeaten after four matches under new head coach Gregg Berhalter, though they were under the cosh at times in the second half against the Copa America champions.
Pulisic, who will see out the season at Borussia Dortmund before moving to Chelsea, showed his class with the opening goal.
Put through by a deft Gyasi Zardes pass that sliced the Chile defence open, Pulisic calmly dinked the ball over onrushing goalkeeper Gabriel Arias.
The effort made Pulisic, at 20 years and 189 days, the youngest to score 10 goals for the national team, besting the previous mark held by Jozy Altidore (20 years, 337 days), U.S. Soccer figures showed.
Pulisic sustained a right quad injury late in the first half and was substituted.
(Reporting by Andrew Both in Cary, North Carolina; Editing by Peter Rutherford)
