The district narrowly voted for George W. Bush in 2000 (due mainly to Ralph Nader being on the ballot), John Kerry in 2004, and Hillary Clinton by 0.1 percentage point in 2016.

As permitted by Citizens United v. Federal Election Commission, a Super PAC group called The Concerned Taxpayers of America paid $300,000 for ads attacking DeFazio.

According to Dan Eggen at The Washington Post, the group said "it was formed in September 'to engage citizens from every walk of life and political affiliation' in the fight against 'runaway spending.'"

DeFazio faced a challenge in 2020 from Alek Skarlatos, a Roseburg High School graduate, a former Oregon National Guard soldier who helped subdue a terrorist in the 2015 Thalys train attack.

In 1992, he co-founded the Congressional Progressive Caucus with Bernie Sanders, Ron Dellums, Lane Evans, Thomas Andrews, and Maxine Waters,[23] and was its chair from 2003 to 2005.

During the 1999 World Trade Organization meetings in Seattle, DeFazio marched with protesters who opposed the WTO's new economic globalization policies.

During his time on the committee, he has served as chair or ranking member of four of the six subcommittees: Aviation, Coast Guard and Maritime Transportation, Highways and Transit, and Water Resources and Environment.

[26] This bill invested $1.5 trillion in highways, rail, transit, airports, ports and harbors, wastewater and drinking water infrastructure, brownfields, broadband, and more.

DeFazio felt shunted aside when Senate negotiators secured a deal on the Infrastructure Investment and Jobs Act which became law largely without input from the House.

[27][28] DeFazio eventually supported and helped pass the Infrastructure Investment and Jobs Act and joined President Biden a number of times to promote it.

[29][30] As chair of the House Transportation and Infrastructure Committee, DeFazio led an investigation into the causes of the crashes of two Boeing 737 MAX planes, which resulted in 346 deaths.

DeFazio helped pass comprehensive aircraft certification reform and safety legislation in the wake of his committee's report[32] as part of the Consolidated Appropriations Act, 2021,[33][34] which President Donald Trump signed into law on December 27, 2020.

[35][36] In October 2011, DeFazio demanded that the U.S. Department of Labor strengthen restrictions on the hiring of foreign guest workers for forestry jobs intended for unemployed U.S.

[38] In January 2018, DeFazio's guest for the State of the Union Address was Jesus Narvaez, a "Dreamer", DACA activist, and member of Movimiento Estudiantil Chicanx de Aztlán (MEChA).

[43] He has consistently voted against the Patriot Act, including its inception after 9/11 and the recurring reauthorization bills, arguing that it infringes on Americans' civil rights.

In 2015, DeFazio was one of 19 members of Congress to sign a letter urging Secretary of State John Kerry to "prioritize the human rights of Palestinian children living in the Occupied West Bank in the bilateral relationship with the Government of Israel."

[53] In 2008, DeFazio and Representative Pete Stark signed a letter to House Speaker Nancy Pelosi proposing a 0.25% transaction tax on all trades in financial instruments, including stocks, options, and futures.

[59] DeFazio made headlines in mid-November 2009 when he suggested in an interview with MSNBC commentator Ed Schultz that Obama should fire Treasury Secretary Timothy Geithner and National Economic Council Director Lawrence Summers.

A year later he called for the impeachment of Chief Justice John Roberts because of the Supreme Court ruling in Citizens United v. Federal Election Commission.

In December 2010, he told CNN that the White House was "putting on tremendous pressure" about legislation extending the Bush tax cuts, with Obama "making phone calls saying this is the end of his presidency if he doesn't get this bad deal."

[64] DeFazio, Representative Dennis Kucinich and Senator Bernie Sanders said that it would be good for the Democratic Party if Obama faced a meaningful primary in which all the issues would be aired out.

[65] In October 2011, Think Progress noted that DeFazio was echoing the demands of the Occupy Wall Street protesters by proposing to tax the trading of stocks, bonds, and derivatives.

[68][69] DeFazio argued that the bill would not solve the true cause of high gas prices, which he blamed on "Big Oil in the United States and speculation on Wall Street".