Rounds' victory was one of South Dakota's greatest political upsets. Until late in 2001, then-Congressman John Thune was the front-runner for the nomination. When Thune passed on the race in order to challenge Senator Tim Johnson, state Attorney General Mark Barnett and former Lieutenant Governor Steve T. Kirby quickly became candidates. Rounds declared his candidacy late, in December 2001 and was out-raised and outspent ten-to-one by each of his opponents.
However, the contest between Kirby and Barnett soon became very negative and "dirty". Barnett attacked Kirby for not investing in companies based in South Dakota and for his involvement with Collagenesis, a company which removed skin from donated human cadavers and processed them for use. It became the subject of a massive scandal when it was revealed that the company was using the skins for much more lucrative cosmetic surgery like lip and penis enhancements while burn victims "lie waiting in hospitals as nurses scour the country for skin to cover their wounds, even though skin is in plentiful supply for plastic surgeons". Kirby invested in the company after the scandal broke and Barnett attacked him for it in television advertisements. However, the advertisements backfired because "the claims were so outlandish, that people thought for sure that they were exaggerated or completely fabricated."
As the two front-runners concentrated on attacking each other, Rounds insisted on running a positive campaign and was not attacked by his opponents. Rounds' positive image and extensive knowledge of state government won him many supporters who were alienated by the front-runners. On the day of the primary election, Rounds won a stunning victory, with 44.3% of the vote to Barnett's 29.5% and Kirby's 26.1%.