Sam Brownback was born on September 12, 1956, in Garnett, Kansas, to Nancy (Cowden) and Glen Robert Brownback. He was raised in a farming family in Parker, Kansas. Some of Brownback's German-American ancestors settled in Kansas after leaving Pennsylvania following the Civil War. Throughout his youth, Brownback was involved the FFA (formerly the Future Farmers of America), serving as President of his local and state FFA chapters, and as national FFA vice President from 1976 to 1977.

While at Kansas State University, Brownback was elected student body President and became a member of the Alpha Gamma Rho agricultural fraternity. After graduating from college in 1979, he spent about a year working as a radio broadcaster for the now-defunct KSAC farm department, hosting a weekly half-hour show. Brownback received his J.D. from the University of Kansas in 1982.

Brownback was an attorney in Manhattan, Kansas, before becoming the Kansas Secretary of Agriculture on September 18, 1986. In 1990, he was accepted into the White House Fellow program and detailed to the Office of the U.S. Trade Representative from 1990 to 1991. Brownback then returned to Kansas to resume his position as Secretary of Agriculture. He left his post on July 30, 1993. He was elected to the U.S. House of Representatives in 1994 and ran in the 1996 special election for the U.S. Senate seat recently vacated by Bob Dole, beating appointed Republican Sheila Frahm.

Brownback, while U.S. Senator in the mid-1990s, hired Paul Ryan as his chief legislative Director. Ryan later became a member of Congress, vice-presidential candidate, and then Speaker of the U.S. House of Representatives.

Brownback is married to Mary Brownback (née Stauffer), whose family owned and operated Stauffer Communications until its sale in 1995. They have five children: Abby, Andy, Elizabeth, Mark, and Jenna. Two of their children are adopted. A former evangelical Christian, Brownback converted to Catholicism in 2002, and is associated with the conservative denominational organization, Opus Dei, but still sometimes attends an evangelical church with his family.

In 1996, as a member of the House of Representatives, Brownback voted for the Defense of Marriage Act, which defined marriage for purposes of federal law as the union between a man and a woman. Brownback has stated that he believes homosexuality to be immoral as a violation of both Catholic doctrine and natural law. He has voted against gay rights, receiving zeros in four of the last five scorecards as a U.S. senator from the Human Rights Campaign. He opposes both same-sex marriage and same-sex civil unions. He opposes adding sexual orientation and gender identity to federal laws that address hate crime. He has declined to state a position on homosexual adoption, although a candidate for chair of the Kansas Republican Party claims he was blackballed by political operatives affiliated with Brownback for not opposing homosexual adoption. Brownback supported "don't ask, don't tell," the U.S. government's ban on openly homosexual people in the military. Brownback has associated with organizations such as the Family Research Council and American Family Association. Both organizations are listed as anti-gay hate groups by the Southern Poverty Law Center.

On September 3, 1997, Meredith O'Rourke, an employee of Kansas firm Triad Management Services, was deposed by the Senate Committee on Governmental Affairs regarding her activities and observations while providing services for the company relative to fund raising and advertising for Brownback. The deposition claims that Triad circumvented existing campaign Finance laws by channeling donations through Triad, and also bypassed the campaign law with Triad running 'issue ads' during Brownback's first campaign for the Senate.

Tim Keck, chief of staff of Brownback's running mate, Lt. Governor Jeff Colyer, unearthed and publicized a 1998 police report that noted that Davis, 26 and unmarried at the time, had been briefly detained during the raid of a strip club, where he had been taken by his new boss at a law firm that represented the club. Davis was found to have no involvement in the cause for the raid and quickly allowed to leave. The incident and its publication were seen as particularly advantageous for Brownback (who, until then, had trailed badly in polling), as it could be expected to become the focus of a typical 30-second campaign ad used to characterize his opponent.

In 2000, Brownback and Congressman Chris Smith led the effort to enact the Trafficking Victims Protection Act. President Clinton signed the legislation in October 2000. According to Christianity Today, the stronger enforcement increased the number of U.S. federal trafficking cases eightfold in the five years after enactment.

In 2003, Brownback worked with Alliance for Marriage and Traditional Values Coalition to introduce a Senate bill containing the Federal Marriage Amendment, a proposed amendment to the United States Constitution that would federally prohibit same-sex marriage in the United States. The bill was a response to Goodridge v. Department of Public Health, the Massachusetts state court decision finding that same-sex couples had the right to marry in Massachusetts. In reaction to the Goodridge decision, Brownback stated that same-sex marriage threatened the health of American families and culture.

Brownback visited refugee camps in Sudan in 2004 and returned to write a resolution labeling the Darfur conflict as genocide, and has been active on attempting to increase U.S. efforts to resolve the situation short of military intervention. He is an endorser of the Genocide Intervention Network, which called him a "champion of Darfur" in its Darfur scorecard, primarily for his early advocacy of the Darfur Peace and Accountability Act.

Brownback is a lead sponsor of the International Marriage Broker Regulation Act of 2005 and frequently speaks out against the mail-order bride industry.

On June 15, 2006, President George W. Bush signed into law the Broadcast Decency Enforcement Act of 2005 sponsored by Brownback, a former broadcaster himself. The new law stiffens the penalties for each violation of the Act. The Federal Communications Commission will be able to impose fines in the amount of $325,000 for each violation by each station that violates decency standards. The legislation raises the fine by tenfold.

Brownback voted against banning chemical weapons. He voted "yes" on reauthorizing the PATRIOT Act and voted "yes" on extending the PATRIOT Act's wiretap provision. In May 2007, Brownback stated that "Iran is the lead sponsor of terrorism around the world." He supports talks and peaceful measures with Iran, but no formal diplomatic relations.

In 2008, Brownback acknowledged he was considering running for governor in 2010. In January 2009, Brownback officially filed the paperwork to run for governor.

In 2009, Citizens for Responsibility and Ethics in Washington (CREW) filed an ethics complaint in 2009 over a fundraising letter signed by Brownback for a conservative Catholic group which they alleged violated Senate rules by mimicking official Senate letterhead. The letter had targeted five senators for being both Catholic and pro-choice: Maria Cantwell, John Kerry, Robert Menendez, Barbara Mikulski and Patty Murray. A spokesman said Brownback had asked the group to stop sending the letter even before the complaint was filed.

On November 2, 2010, Brownback won over Holland with 63.3% of the vote, replacing Governor Mark Parkinson, who was sworn in after former Governor Kathleen Sebelius resigned from her position and accepted the appointment to US Secretary of Health and Human Services in 2009.

In April 2011, Brownback began work on a Kansas government program to promote marriage, in part through grants to faith-based and secular social Service organizations. In June 2011, the administration revised contract expectations for social work organizations to promote married mother-father families. It explained the change as benefiting children.

In February 2012, the Brownback administration supported a religious freedom bill that would have stopped cities, school districts, universities, and executive agencies from having nondiscrimination laws or policies that covered sexual orientation or gender identity.

In 2013, after oral arguments in United States v. Windsor, the U.S. Supreme Court case striking down part of the Defense of Marriage Act, Brownback publicly reaffirmed his opposition to same-sex marriage.

Throughout his Senate career, Brownback's principal campaign donors were the politically influential libertarian Koch brothers of Kansas, and their enterprises, including Kansas-based Koch Industries—and Brownback was one of the candidates most-heavily funded by the Kochs' campaign donations. Over the course of his political career, they donated hundreds of thousands of dollars to his campaigns.

On February 10, 2015, Brownback issued an executive order rescinding protections for lesbian, gay, bisexual and transgender state workers that was put into place by then-Gov. Kathleen Sebelius eight years previously. In the February 11, 2015, edition of The Daily Show, Comedian Jon Stewart suggested that an internet campaign similar to the campaign for the neologism "santorum", which had lampooned former U.S. Senator Rick Santorum, could introduce a similarly sex-related neologism "brownbacking" in order to embarrass Brownback. The ACLU generally characterized his actions as being "religious freedom to discriminate."

On April 25, 2016, Brownback issued executive orders barring state agencies from facilitating refugee resettlement from Syria and other majority Muslim countries, in concert with the federal Office of Refugee Resettlement (ORR). He maintained they presented security risks. His decision entirely removed the state from the program. The federal Office of Refugee Resettlement served notice that it would instead work directly with local refugee resettlement organizations. Mark Greenberg of the federal Administration for Children and Families said, “If the state were to cease participating in the refugee resettlement program, it would have no effect on the placement of refugees by the State Department in Kansas, or the ORR-funded benefits they can receive." Although states are legally entitled to withdraw from the program, the initial withdrawal for claimed security reasons, is the first in the nation. Micah Kubic, the Kansas ACLU's executive Director said Brownback’s policy removed the state from the process of protecting those seeking safety jeopardized by their religious beliefs, despite such refugees receiving thorough screenings: "It's very sad and very unfortunate that the governor is allowing fear to get in the way of hospitality and traditional Kansas values." Earlier in 2016, Brownback directed state agencies to use the State Department’s list of state-sponsors of terrorism to exclude refugees whose presence might constitute security risks. Refugees who were fleeing danger in Iran, Sudan and Syria were singled out for exclusion. Thanks to Brownback's initiative, Kansas would lose about $2.2 million annually that had been provided to support resettlement agencies. The state had been working with three such agencies, among them Catholic Charities of Northeast Kansas, to in making appropriate placements. In the seven months preceding his order, 354 refugees from all countries have been resettled in Kansas, she said, with thirteen Syrians placed in the Wichita or Kansas City areas of the state in prior sixteen months. Democratic Representative Jim Ward, from Wichita, characterized Brownback’s announcement as "a distraction," intended solely for political purposes, as Kansas faced a $290 million budget deficit.

In March 2017, it was reported that Brownback was being considered by President Donald Trump to be appointed as his U.S. Ambassador to the U.N. for Food and Agriculture in Rome, and as the U.S. Ambassador-at-Large for International Religious Freedom in Washington, DC. On July 26, 2017, the White House issued a statement that Brownback would be nominated as the U.S. Ambassador-at-Large for International Religious Freedom. If confirmed, Brownback would become the first Catholic to serve in the role. As a senator in 1998, Brownback sponsored the legislation that first created the office.

As of the end of the 2017 session, Brownback's Ambassadorial nomination had not come up for a confirmation vote. As it failed to receive unanimous support for it to carry over to 2018 for approval, it required renomination to come to a vote. He was renominated on January 8, 2018, and was confirmed two weeks later on January 24, 2018. On January 25, Brownback submitted his resignation as governor, effective January 31, 2018, and Jeff Colyer will then be sworn in as governor.

Responding to criticism of Keck's involvement in the campaign, Brownback spokesman Paul Milburn commented that it was legal to use taxpayer-paid staff to campaign, responding directly to the controversy, saying, "Paul Davis must have spent too much time in VIP rooms at strip clubs back in law school...", because he "... should know full well that the law allows personal staff of the governor’s office to work on campaign issues." In Kansas, however, getting records about crimes that law enforcement has investigated is typically difficult. The Legislature closed those records to the public over three decades earlier: If members of the public Desire incident reports and investigative files, they normally have to sue to obtain them, cases sometimes costing $25,000 or more. Media law experts were amazed after learning Montgomery County's sheriff released non-public investigative files from 1998 with just a records request. "That is unusual," said Mike Merriam, media Lawyer for the Kansas Press Association. "They have denied releasing records routinely over and over and over again." Brownback's campaign capitalized on the 16-year-old incident.