Mukasey was noticeably shaking during his speech before he collapsed shortly before 10:20pm EST (03:20 GMT Friday).
He "just started shaking and he collapsed", Kevin O'Connor, the assistant attorney-general, the department's number three official, said.
The incident happened 15 to 20 minutes into a speech about the Bush administration's successes in combating terrorism when he began slurring his words and lost consciousness.
His security detail called for an ambulance.
Prior to the appointment, Mukasey had carved out a no-nonsense reputation during his 18 years as a federal judge in New York, and oversaw several cases including the 1993 trial of Omar Abdel-Rahman, the Blind Sheikh, who was sentenced to life in jail for plotting to blow up New York landmarks.