Jones's most prominent cases were the successful prosecution of two Ku Klux Klan members for the 1963 Birmingham church bombing that killed four African-American girls and the indictment of domestic terrorist Eric Rudolph.

Jones announced his candidacy for United States Senate in the 2017 special election following the resignation of Republican incumbent Jeff Sessions to become U.S. Attorney General.

After winning the Democratic primary in August, he faced former Alabama Supreme Court Justice Roy Moore in the general election.

Jones was considered a fairly moderate Democrat, who supported reproductive and LGBT rights but demonstrated a willingness to work with Republicans and split with his party on certain issues.

[20][21] Jones prosecuted Thomas Edwin Blanton Jr. and Bobby Frank Cherry, two members of the Ku Klux Klan, for their roles in the 1963 16th Street Baptist Church bombing.

[27] Jones left office in 2001 and returned to private practice, joining the law firm of Haskell Slaughter Young & Rediker.

[32] Also in 2007, Jones testified before the United States House Committee on the Judiciary about the importance of reexamining crimes of the Civil Rights Era.

"[38] Despite his successful prosecution of the 16th Street Baptist Church Bombing case, Jones was not well-known statewide and had low name recognition.

[40] On May 11, 2017, Jones announced his candidacy for that year's U.S. Senate special election, running for the seat left open when Sessions was appointed Attorney General.

[54][55] Jones was one of five Democratic senators who voted for the continuing resolution that failed to pass and consequently led to the January 2018 United States federal government shutdown.

[58] In September 2019, after the House launched an impeachment inquiry against President Trump, Jones urged caution on the part of the media and his colleagues because his experience with law had led him to believe that it was "very unlikely there's going to be an absolute smoking gun on either side".

Jones voted against the Pain-Capable Unborn Child Protection Act, which prohibits abortion after 20 weeks except in cases of rape, incest or danger to the pregnant woman's health.

"[85] On December 11, 2018, Jones voted for the conference farm bill, which included his provisions for farmers, rural health, wastewater infrastructure, and high-speed internet.

[86] In May 2019, he co-sponsored the Transporting Livestock Across America Safely Act, a bipartisan bill introduced by Ben Sasse and Jon Tester intended to reform hours of service for livestock haulers by authorizing drivers to have the flexibility to rest at any point during their trip without it being counted against their hours of service and exempting loading and unloading times from the calculation of driving time.

[88] In December 2018, Jones voted for the First Step Act, legislation aimed at reducing recidivism rates among federal prisoners by expanding job training and other programs in addition to expanding early-release programs and modifying sentencing laws such as mandatory minimum sentences for nonviolent drug offenders, "to more equitably punish drug offenders.

[73] In June 2019, along with Democrat Mark Warner and Republicans Tom Cotton and Mike Rounds, Jones introduced the Improving Laundering Laws and Increasing Comprehensive Information Tracking of Criminal Activity in Shell Holdings (ILLICIT CASH) Act, a bill mandating that shell companies disclose their real owners to the United States Department of the Treasury and updating outdated federal anti-money laundering laws by bettering communications among law enforcement, regulatory agencies, the financial industry, and the industry and regulators of advanced technology.

[90] In March 2018, Jones voted against Bernie Sanders's and Chris Murphy's resolution to end U.S. support for the Saudi Arabian-led intervention in Yemen.

[91] In an interview with The Birmingham News, Jones said he favored increasing defense spending, saying it would boost Alabama's local economy, particularly in the areas around NASA's Marshall Space Flight Center and the U.S. Army's Redstone Arsenal, and protect the United States from foreign threats.

[95] In October 2019, Jones was one of six senators to sign a bipartisan letter to President Trump calling on him to "urge Turkey to end their offensive and find a way to a peaceful resolution while supporting our Kurdish partners to ensure regional stability" and arguing that to leave Syria without installing protections for American allies would endanger both them and the US.

[102] On September 19, 2019, Jones took to the Senate floor to request unanimous consent to pass legislation that would further the $255 million in federal funding for minority-serving colleges and universities ahead of its expiration date in weeks.

[108] In March 2018, Jones was one of 10 senators to sign a letter to Chairman of the United States Senate Committee on Health, Education, Labor and Pensions Lamar Alexander and ranking Democrat Patty Murray requesting they schedule a hearing on the causes and remedies of mass shootings in the wake of the Stoneman Douglas High School shooting.

[109] In 2018, Jones co-sponsored the NICS Denial Notification Act,[110] legislation developed in the aftermath of the Stoneman Douglas High School shooting that would require federal authorities to inform states within a day after a person failing the National Instant Criminal Background Check System attempts to buy a firearm.

[73] In January 2018, Jones was one of six Democrats to join most Republicans in voting to confirm Alex Azar, Trump's nominee for Secretary of Health and Human Services.

[113] In December 2018, Jones was one of 42 senators to sign a letter to Trump administration officials Alex Azar, Seema Verma, and Steve Mnuchin arguing that the administration was improperly using Section 1332 of the Affordable Care Act to authorize states to "increase health care costs for millions of consumers while weakening protections for individuals with preexisting conditions".

[115] In January 2019, Jones was one of six Democratic senators to introduce the American Miners Act of 2019, a bill that would amend the Surface Mining Control and Reclamation Act of 1977 to swap funds in excess of the amounts needed to meet existing obligations under the Abandoned Mine Land fund to the 1974 Pension Plan as part of an effort to prevent its insolvency as a result of coal company bankruptcies and the 2008 financial crisis.

It also increased the Black Lung Disability Trust Fund tax and ensured that miners affected by the 2018 coal company bankruptcies would not lose their health care.

[118] In September 2019, amid discussions to prevent a government shutdown, Jones was one of six Democratic senators to sign a letter to congressional leadership advocating the passage of legislation to permanently fund health care and pension benefits for retired coal miners as "families in Virginia, West Virginia, Wyoming, Alabama, Colorado, North Dakota and New Mexico" would start to receive notifications of health care termination by the end of the following month.

[128] He opposed the Tax Cuts and Jobs Act of 2017, calling it fiscally irresponsible and skewed to benefit the wealthy while ignoring or hurting the middle class.

Jones said the process currently led by the Commerce Department to investigate whether a trading partner is undermining U.S. national security had "been misused to target important job-creating industries in Alabama like auto manufacturing" and that the bill would refocus "efforts on punishing bad actors, rather than hurting American manufacturers, workers, and consumers.

[134] In December 2018, Jones was one of 21 senators to sign a letter to United States Secretary of Veterans Affairs Robert Wilkie calling it "appalling that the VA is not conducting oversight of its own outreach efforts" in spite of suicide prevention being the VA's highest clinical priority and requesting that Wilkie "consult with experts with proven track records of successful public and mental health outreach campaigns with a particular emphasis on how those individuals measure success".