Cassel was sacked by Brandon Mebane on the first passing play. He appeared to have a problem with his left leg, but came off the field unassisted before being replaced by Tyler Thigpen. A team spokesman said Cassel's return was questionable.
Cassel signed a long-term contract with a guarantee of $28 million after being acquired in an offseason trade with New England.
Cornerback Brandon Flowers and wide receiver Devard Darling also left in the first half with injuries.
Flowers, whose 28-yard interception return gave the Chiefs a 7-0 lead in the first quarter, came out a short time later with an apparent shoulder injury. Late in the second quarter, Darling was helped off the field with what appeared to be an injured left leg.
Chiefs starting safety Jarrad Page was not in uniform, though he had been expected to play. A Chiefs spokesman said he did not know what Page's status was.