Thune, who was considered a rising star in his party, ran against Tim Johnson, who narrowly won his first senate election in 1996. Thune launched a television advertising campaign mentioning al Qaeda and Saddam Hussein, contending that both are seeking nuclear weapons and that this country needs a missile defense system, something Johnson voted against 29 times and that Thune supports. The incumbent attacked Thune for politicizing national security. President George W. Bush campaigned for Thune in late October. More than $20 million was spent in the election. Both candidates had raised over $5 million each.
Johnson narrowly prevailed over Thune by a mere 524 votes. Despite the extreme closeness of the election, Thune did not contest the results and conceded defeat on the late afternoon of November 9. Johnson's narrow victory may be attributed to Minnehaha County home of Sioux Falls. Thune also underperformed in typically Republican areas. Johnson was sworn in for a second term on January 3, 2003. Johnson would go on to easily win a third term in 2008.