Kirk is "a man who can make a real difference in the lives of American families," Vice President Joe Biden said shortly before administering the oath of office.
"He's like a bulldog. He doesn't let anything go … (He will) help inspire a new environment of basic fairness in our trade relationships."
Kirk's nomination came into question after a Senate Finance Committee found that he had failed to report as income $37,750 in honoraria collected for 16 speaking engagements between 2005 and 2007.
Kirk paid the $9,975 he owed from amended returns.
The Senate voted Wednesday to confirm Kirk.
The former mayor promises to help strike a new balance between a commitment to free trade and concerns relating to environmental and labor standards.