Kirk lost re-election to a second full term[3] to Tammy Duckworth, the U.S. representative from Illinois's 8th congressional district and a decorated combat veteran of the Iraq War.

[4] In June 2013 he confirmed that he was "planning" to run for re-election,[5][6] but there was speculation that he might retire,[7] particularly in the wake of the departure of several of his senior staff.

Representatives Bob Dold, Adam Kinzinger, Aaron Schock, and Peter Roskam, State Senators Jason Barickman and Christine Radogno, hedge fund manager and founder and CEO of Citadel LLC Kenneth C. Griffin, and businesswoman Beth Christie.

[88][89] Kirk had multiple factors working against him, as no Republican had won an Illinois US Senate race during a presidential election year since 1972, and he had made a number of gaffes during the campaign.

He had exaggerated his Iraq War record on his campaign website,[94] and during a debate, Kirk made a racially charged remark about Duckworth's familial military background.

Due to these factors, Kirk alienated the Democratic, Independent, and Republican voters whom he had previously won over in his 2010 campaign.

Unusually, the normally Republican-leaning editorial board of the Chicago Tribune endorsed Duckworth, as they believed that the health problems that Kirk had suffered as a result of his stroke made him a less effective Senator.

Representatives Labor unions Newspapers Organizations with Andrea Zopp with Lisa Madigan with Michelle Obama with Pat Quinn The result was a landslide victory for Tammy Duckworth.

Duckworth performed extremely well in the heavily populated and strongly Democratic Cook County, home of Chicago.