She ran in the Republican primary in the 2018 Illinois gubernatorial election, narrowly losing to incumbent governor Bruce Rauner.

[7] Ives has said she made her decision to challenge Governor Bruce Rauner in the 2018 Republican primary after Rauner signed HB-40 into law, which ensures that abortion remains legal in Illinois even though the U.S. Supreme Court overturned Roe v. Wade, while also enabling Medicaid and state-employee health insurance to pay for abortions, in September 2017.

[14] In March 2013, Ives said in an interview that same-sex marriages are a "completely disordered relationship" and said LGBT people were trying to "weasel their way" into acceptability.

"[16] When a law authorizing gay marriage passed the Illinois General Assembly, in November 2013, Ives said, "The fact is that this bill is the worst in the U.S. for protecting religious liberty.

[19] In March 2016, a Chicago man was arrested for a felony after making two threatening phone calls to Ives over her views on same-sex marriage.

[22] Ives opposed a 2017 bill that would make it easier for transgender people to change their birth certificates to reflect their gender identity.

[25][26] In May 2016, Ives voted against the extending the sunset date of the program that legalized cannabis for medical purposes.

"[28] In May 2017, Ives voted against legislation (Senate Bill 81) in May 2017 that would have raised the minimum wage in Illinois to $15 per hour by the year 2022.

Ives was opposed in the primary by Evelyn Sanguinetti, who dropped out of the race in October 2019, and surgeon Jay Kinzler.

[37][38][39][40] In March 2020, Ives won the Republican nomination, setting up a general election against Democratic incumbent Sean Casten.