After seven-term Republican incumbent Ernest Istook announced that he would retire from his seat to run for governor, Fallin declared her candidacy for Oklahoma's 5th congressional district, where she was elected to two terms in the U.S. House of Representatives, serving from 2007 to 2011.

[6] In 1992, Oklahoma became one of the first five states in the nation to enact anti-stalking legislation when Fallin authored and introduced HB 2291, which made it illegal to stalk or harass people.

Early in her tenure, the Alfred P. Murrah Federal Building, located in Oklahoma City, was bombed, killing 168 people in what became the worst case of domestic terrorism in United States history; Fallin led a task force to rebuild the childcare center that was lost in the attack.

Lieutenant Governor-elect Jari Askins was appointed by Oklahoma Governor Brad Henry to fill the remaining days of Fallin's term.

Members of that task force include BancFirst CEO David Rainbolt and former Walters Administration Secretary of Agriculture Gary Sherrer.

Former Keating Administration Secretary of Energy Robert J. Sullivan, Jr. serves as the director of the Taskforce as the Special Advisor to the Governor on Economic Development.

Fallin pushed strongly for the execution of convicted murderer Clayton Lockett to proceed in spite of the lack of tested drugs to use for lethal injection.

When the Oklahoma State Supreme Court granted a stay of execution, Fallin immediately overruled it, leading some political commentators to raise the possibility of a constitutional crisis surrounding the separation of powers.

[42] Robert Patton, her director of corrections, resigned, and despite an Oklahoma conflict of interest law, was hired as a deputy warden by GEO Group whose contract he had overseen.

[46] In 2017, Fallin praised a package of bills passed by the state House and state Senate; the bills, which passed unanimously or by broad margins, would, among other things, allow nonviolent offenders sentenced to life imprisonment to petition for a sentence modification after ten years in prison; expand diversion programs that steer convicted persons from prison to treatment and supervision; mandate "the creation of individualized plans for inmates to help them better reintegrate into society" after release from prison; and establish an oversight council to track the effectiveness of reform initiatives.

[48] This package of bills, supported by Fallin and recommended by the Task Force, would lower sentences for nonviolent drug crimes, allow more elderly prisoners to be paroled, and expand diversion programs.

Fallin initially refused to follow the court order, expressing the view that the ruling was incorrect and that the state would petition for a rehearing of the case.

[54][55] The court's ruling was subsequently upheld, and in October 2015 the monument was quietly removed from Capitol grounds to a private property several blocks away.

[70] The partial repeal of the state's earned income tax credit was supported by legislative Republicans, who wanted additional revenue for the state to close a shortfall, and opposed by legislative Democrats and the Oklahoma Policy Institute, who argued that it was wrong to eliminate a tax credit that helped working poor Oklahomans.

[78] In April 2015, Fallin signed into law a measure banning a common second-trimester abortion procedure, dilation and evacuation, except when necessary to save the life of the woman.

[80] In May 2016, Fallin vetoed a bill passed by the Oklahoma State Legislature that would have made it a felony, punishable by up to three years in prison, to perform an abortion, except in instances to save the life of the mother.

In a statement, Fallin's office said: "The bill is so ambiguous and so vague that doctors cannot be certain what medical circumstances would be considered 'necessary to preserve the life of the mother.

[86] Fallin later backed down after U.S. Secretary of Defense Chuck Hagel stated that Oklahoma would be in violation of federal law for refusing to recognize the relationships.

[88] In 2014, Fallin vetoed a bill that would have required sheriffs and police chief to approve individuals' "applications for tax stamps for items such as silencers, suppressors, short-barreled rifles and shotguns, and automatic weapons."

[90] In 2018, Fallin vetoed legislation to authorize adults to publicly carry guns without permit or training, prompting the NRA to criticize her.

[88][91] Fallin is part of a group of Republican governors who have said that they will refuse to comply with Environmental Protection Agency regulations to reduce carbon emissions and combat climate change.

[92][93][94] In April 2015, Fallin issued an executive order prohibiting the Oklahoma Department of Environmental Quality and other state agencies from creating an emissions-reduction strategy under the Clean Power Plan,[93][94] becoming the first governor to do so.

[94] In a proclamation in September 2016, Fallin declared October 13, 2016, to be Oilfield Prayer Day, calling upon Christians to "thank God for the blessing created by the oil and natural gas industry and to seek His wisdom and ask for protection.

The controversy arose over the Board of Education rejecting three senior staff members of Oklahoma State Superintendent of Public Instruction Janet Barresi.

[105] In May 2015, Fallin signed a bill for a $25 million bond proposal to complete the Native American Cultural Center and Museum, a project already underway.

[106] In March 2017, Fallin approved of the Shawnee Tribe's plan to build a $25 million casino close to Guymon in the Oklahoma Panhandle.

[107][108] In the June 2018 primary election, Oklahoma voters approved State Question 788, a ballot measure that legalized the growth, possession, sale, and use of marijuana for medicinal purposes, and provided that physicians could broadly prescribe it for various conditions.

[109] On July 11, 2018, soon after the measure passed, Fallin signed stringent new emergency rules adopted by the Oklahoma Board of Health to prohibit the sale of marijuana in smokeable form and to require that a pharmacist be on-site at dispensaries during operating hours.

[110][111] These regulations angered marijuana activists,[110] drawing bipartisan opposition in the state and fueling renewed calls for a special session of the legislature.

[117] They have a total of six children in their blended family, one of whom—model, makeup artist, and musician Christina Fallin—was described as "the most interesting governor's daughter in the country" by a 2014 Washington Post article.