His United States Senate campaign

In 2004, Obama decided to run for the U.S. Senate seat held by Sen. Peter Fitzgerald. In the Democratic primary, he trailed business tycoon Blair Hull and Illinois Comptroller Dan Hynes. However, Hull was soon embroiled by allegations of domestic abuse. As Obama's name recognition rose, voters took a liking to the bright, charismatic senator. He won decisively in the March primary, dispatching the other six candidates easily, and winning more than 50 percent of the vote.

Entering the U.S. Senate campaign, Obama had become a national Democratic star. He squared off against former Goldman Sachs partner and teacher Jack Ryan, the winner of the Republican primary. Ryan trailed Obama in the polls, and Obama opened up a twenty point lead after the media brought attention to the fact that Ryan had assigned an aide to stalk Obama. However, during the campaign, a California court ruling opened custody files from Ryan's divorce from actress Jeri Ryan, in which she alleged that he had brought her without her knowledge to sex clubs, intending for her to have sex with him in public. The files, which were part of the custody proceedings regarding the Ryans' young son, were opened as a result of a lawsuit brought by the Chicago Tribune and WLS-TV, a local ABC affiliate. Ryan had insisted that there was nothing damaging in the files, and many Republican leaders openly questioned Ryan's integrity following the release. Ryan was forced to leave the race on June 25, 2004, leaving Obama without an opponent.

Former Chicago Bears coach Mike Ditka had considered running as a Republican to replace Ryan, but opted not to because of family and business considerations. After many more candidates turned down the Illinois GOP, Republican state Chairwoman Judy Baar Topinka announced two possible replacements: Alan Keyes, a former ambassador residing in Maryland, and Andrea Barthwell, a DEA official. After much deliberation, Keyes was chosen, and he officially accepted the nomination on August 8. He had gained much attention as a conservative firebrand in his unsuccessful presidential campaigns in 1996 and 2000. This was widely viewed as a victory for the more conservative wing of the party, and a loss for the more moderate Topinka.

Keyes, a black conservative Republican, had an uphill battle, as Obama had high popularity across the state and Keyes had no ties to Illinois politics. During the time when he had no opponent, Obama campaigned across more conservative downstate areas that ordinarily served as the base for the Republican nominee. A Marylander, Keyes had established legal residency in Illinois with the nomination, the only requirement to run for office. The Chicago Tribune sarcastically greeted Keyes by editorializing: "Mr. Keyes may have noticed a large body of water as he flew into O'Hare. That is called Lake Michigan."

Keyes's previous comments about U.S. Senator and former First Lady Hillary Clinton's run for Senate in New York, ("I deeply resent the destruction of federalism represented by Hillary Clinton's willingness to go into a state she doesn't even live in and pretend to represent people there, so I certainly wouldn't imitate it.") led many to call Keyes hypocritical. Keyes often rebutted this by pointing out that he was invited to run for the position in Illinois, whereas he claimed Clinton was not.

After a campaign in which Keyes called Obama's position on abortion "the slave-holder's position" and also claimed that Jesus would not vote for Obama, Obama won handily in the general election. Obama received 70% of the popular vote, to Keyes' 27%.