McCaskill spent her early childhood in the small Missouri town of Houston, later moving to Lebanon, and eventually Columbia.

[7] From the time she graduated from law school in 1978 until her exit from the U.S. Senate in January 2019, McCaskill spent all but three years of her professional career in the public sector.

In February 1991, she testified in favor of a Missouri Senate bill that would prohibit a man accused of raping his wife from using marriage as a defense.

When McCaskill ran for reelection in 2002, the winner of the Republican Party primary was Al Hanson, who had previously been incarcerated for fraud.

Then, in a television interview on August 12, Akin claimed that women who were the victims of what he described as "legitimate rape" rarely ended up pregnant.

In August 2015, McCaskill penned a Politico article describing how she indirectly helped Akin—who she believed would make a weak general election candidate—win the Republican primary.

[34] Less than three weeks before the November general election, conservative group Project Veritas released secretly recorded video footage of statements by McCaskill and her campaign staff that appeared to differ from their public stances on several issues.

[38] McCaskill later said that the "spectacle" her fellow Democrats created during the confirmation hearings of Brett Kavanaugh's nomination to the U.S. Supreme Court also played a factor in her defeat.

[47][48] In January 2008, McCaskill endorsed then-Senator Barack Obama in his campaign for the Democratic nomination for president, making her one of the first Senators to do so.

[57] In 2010, McCaskill voted for the DREAM Act, which would have given undocumented immigrants who entered the United States as children a pathway to citizenship provided that they fulfilled certain conditions.

"[74] At each event during her 2018 re-election bid campaign, McCaskill asked attendees with preexisting conditions to stand up, and vowed to keep in place health insurance protections for such individuals.

[75][76] McCaskill received an "F" rating from the NRA Political Victory Fund (NRA-PVF) for not supporting their view of Second Amendment rights and opposing all right-to-carry legislation.

[77] She voted for expanded background checks and co-sponsored the "Feinstein Amendment," a proposal that would have made it illegal for individuals on the terror watchlist to purchase guns.

[78] In January 2016, McCaskill was one of eighteen senators to sign a letter to Thad Cochran and Barbara Mikulski requesting that the Labor, Health and Education subcommittee hold a hearing on whether to allow the Centers for Disease Control and Prevention (CDC) to fund a study of gun violence and "the annual appropriations rider that some have interpreted as preventing it" with taxpayer dollars.

[81] During a 2013 congressional hearing, McCaskill asked Homeland Security Secretary Janet Napolitano: "Based on the evidence at this point, is there any difference between Sandy Hook and Boston other than the choice of weapon?"

[82] In October 2017, in the midst of a flurry of news reports about sexual assaults by politicians and other celebrities, McCaskill said on Meet the Press that while serving in the state legislature, she had asked the House Speaker, Bob F. Griffin, to discuss a bill she was sponsoring.

"[89] McCaskill apologized for using the word transsexuals, which she called a "hurtful term", the next day in a tweet, saying she was "tired" but admitting that is "never a good excuse".

[90] In October 2017, McCaskill was one of four Democrats who voted to confirm FCC Commissioner Ajit Pai,[91] who announced the plan to reverse net neutrality rules earlier that year.

[93] According to Ars Technica, "it's common for [FCC] commissioners to get broad bi-partisan support in the Senate even if their policies are opposed by one of the two major parties.

"[94] In June 2017, McCaskill co-sponsored the Israel Anti-Boycott Act, Senate Bill 720, which made it a federal crime, punishable by a maximum sentence of 20 years imprisonment,[95] for Americans to encourage or participate in internationally sponsored boycotts against Israel and Israeli settlements in the occupied Palestinian territories if protesting actions by the Israeli government.

[97] She said, "Misinformation campaigns intended only to suppress the vote and disenfranchise Missourians are crimes that run counter to our democratic values.

[101] On March 16, 2011, McCaskill told reporters that she was "embarrassed" about revelations that her office had used taxpayer money for the senator's use of a private airplane she co-owned with her husband and friends.

According to a government audit, the plane was used for 90 flights taken between Washington, D.C., and her home in suburban St. Louis, as well as to numerous sites around the state of Missouri.

"[103] On March 21, 2011, Politico reported that McCaskill and her husband had failed to pay more than $280,000 in property taxes on the plane and were planning to sell it.

[105] It was stored at Spirit of St. Louis Airport, McCaskill confirmed, and owned by Timesaver LLC, a Delaware-based limited liability company.

and August 6, 2015 ("Today calls with British, Russian, and German Ambassadors") were exposed, McCaskill recanted her tweet of March 2, blaming Twitter's character limit.

As part of the botched investigation into the Guard Recruiter Assistance Program (G-RAP), false arrest records were added into federal databases after individuals were cleared of charges.

Guardsmen who worked as police officers outside the Guard lost their jobs, concealed weapons permits were revoked, and promotions were inappropriately denied.

[112] In October 2022, McCaskill joined the Council for Responsible Social Media project launched by Issue One to address the negative mental, civic, and public health impacts of social media in the United States co-chaired by former House Democratic Caucus Leader Dick Gephardt and former Massachusetts Lieutenant Governor Kerry Healey.

on National Public Radio, McCaskill spoke about a vacation early in her career as a lawyer, where she was a contestant on High Rollers.