Several moments after the England man was withdrawn, and after United opened the scoring, Gunners keeper Wojciech Szczesny was also forced off.
Wilshere was caught on his left foot in a challenge by United defender Paddy McNair shortly after half-time, and spent several minutes on the ground before getting to his feet to walk to the sidelines.
He swiftly returned to the action but looked in severe discomfort, hobbling around the pitch before dropping to the ground once again.
The England midfielder was then replaced by Santi Cazorla, while Damian Martínez came on for Szczesny.
The injury was similar to one suffered by Luke Shaw in the first half. The Manchester United defender, who passed a late fitness test, turned his ankle in a clash with Alex Oxlade-Chamberlain.
He too returned to the pitch but was eventually forced off after colliding with Wilshere.
Wilshere could also have been sent off in the first half for thrusting his head at Marouane Fellaini.