Ziyech gave the Blues the lead in the 27th minute, converting a cross from Kai Havertz from close range.
Just minutes later, the Moroccan star had to be taken off after a painful-looking incident during a Villarreal corner kick.
Just as the first half was drawing to a close, Ziyech appeared to be in a great deal of pain after an awkward landing while defending a corner kick.
Ziyech was holding his shoulder and had to be replaced by Christian Pulisic in the 43rd minute.
The Morocco star was later seen on the Chelsea bench with a sling on his arm.
Ziyech has been in outstanding form for Chelsea during pre-season and looked to be a candidate to start Saturday’s Premier League opener against Crystal Palace.
After Chelsea won the Super Cup in penalties against the Liga side, manager Thomas Tuchel offered a pessimistic update on Ziyech.
“If you take a player out during the first half it is serious,” Tuchel told BT Sport. “Unfortunately, because he is a decisive player in the last games.”
Ziyech had an up-and-down campaign at Stamford Bridge in 2020-21, his first season with the club after joining from Ajax.
The 28-year-old managed just 15 starts in the Premier League and three in the Champions League as he battled injuries and strong competition for places at Stamford Bridge.
Ziyech did manage to score six goals in 39 total games, as Chelsea lifted the Champions League.