On May 12, 2023, President Joe Biden nominated Markell to serve as the United States ambassador to Italy and San Marino.

Markell was first elected state treasurer of Delaware in 1998, unseating four-term Republican incumbent Janet Rzewnicki, and was re-elected in 2002 and 2006.

Beginning in the summer of 2007, Markell released fourteen policy papers on issues ranging from energy to health care to education.

[16] After failing to obtain an initial majority in the House of Representatives, Markell's sports betting proposal was approved on a second vote in May 2009.

Current revenues estimates are lower following a decision by the U.S. Third Circuit Court of Appeals banning single game bets.

[17] Several states in similar circumstances were unable to meet their budget deadlines and were forced to cut or close down many government offices and programs.

The FY 2011 budget focuses on job creation and economic development, counteracted by a reduction in the number of state employees.

[21] On July 2, 2009, Markell signed legislation banning discrimination based on sexual orientation in housing, insurance, public accommodations and employment, ending a ten-year battle.

[23] Markell proposed and signed major educational reform initiatives, including abolishing the controversial Delaware Student Testing Program, establishing a pilot program to reward improving schools, and passing legislation to improve transparency and autonomy within school districts.

[24] Markell facilitated the acquisition of the Newark Chrysler plant by the University of Delaware (UD) to build a research and technology campus that may generate both employment and local innovation.

UD President Patrick Harker stated: "Our goal over time is to construct high performance facilities that support the University's Climate Action Plan and restore portions of the land and natural features.

"[25] In March 2010, Delaware placed first out of the 16 finalists in the federal government's grant competition for innovative education reform, making the state eligible to receive as much as $119 million.

Fisker anticipates that the process will create approximately 2,500 jobs and contribute to Delaware's effort to compete in the "green economy.

[29] The refinery became operational in 2011, and Markell and PBF agreed that the company would receive economic development incentives in exchange for providing 600 full-time jobs.

[31] Thanks to the Delaware Strategic Fund, a state program that can provide economic incentives to companies thinking of moving to Delaware, Markell and his economic development team have also succeeded in attracting businesses such as Sanosil International and Testing Machines Inc.[32] In June 2010, Markell signed into law the Business Finder's Fee Tax Credit or "BFF", which provides incentives for companies that bring new jobs to the state.

"The BFF program will make us more effective and efficient by enlisting Delawareans across the state to search for more opportunities to create jobs," said Markell.

[38] Following a legislative task force on election laws and a campaign finance report issued by special prosecutor Norman Veasey, Markell joined with nearly two dozen legislators to introduce a series of six bills to combat corruption and strengthen state campaign finance laws.

The bills, among other goals, would enhance investigative powers for election officials, expand disclosure requirements, and protect "whistleblowers" seeking to expose campaign finance violations.

The proposals included requirements for reporting stolen or lost guns, a ban on certain assault weapons and high capacity magazine, universal background checks, new safeguards against licensing firearms to individuals with serious mental health issues, and a ban on firearms within 1000 feet of a school.

Markell proposes to pay for the new initiative through a series of loans and a small tax on water usage by homeowners, which would average around $45 a year.

[45] In August 2014, Markell signed House Bill 340 that requires school to have updated plans for a variety of emergency situations.

[48] The report found that personal emails from Markell to several of his contributors advised them on the parameters of the campaign laws, information that the donors later used to donate beyond the legal limit.

"[49] Special prosecutor Veasey did not press charges against elected officials as the statute of limitations had expired and they found "no credible evidence" that Markell's campaign had intentionally broken the law; however, multiple donors had previously pleaded guilty for their participation.

The trail features off-road boardwalks and bridges, paved pathways, benches, a bike repair station, and scenic views of the Christiana river's tidal marshes.

[53] On June 23, 2021, President Joe Biden nominated Markell to serve as the United States ambassador to the Organisation for Economic Co-operation and Development.

[55] Markell was sworn in on January 14, 2022, and presented his credentials to OECD Secretary General Mathias Cormann on February 11, 2022.