[6][7][8] After completing his master's degree, Merkley was selected as a Presidential Management Fellow, working at the Office of the Secretary of Defense on the security of American military technology.

Upon his swearing in, Oregon was represented in the Senate by two Democrats (Merkley and Ron Wyden) for the first time since Maurine Brown Neuberger served alongside Morse from 1960 to 1967.

Along with Michigan Senator Carl Levin, he successfully added an amendment, usually called the Volcker Rule, to the Dodd–Frank Wall Street reform bill, which banned high-risk trading inside commercial banking and lending institutions.

Merkley also championed an amendment that banned liar loans, a predatory mortgage practice that played a role in the housing bubble and subsequent financial collapse.

[28] Merkley also championed legislation to give new mothers private space and flexible break times to pump breast milk once they return to work.

[29] In late February 2010, Merkley again made headlines when he unsuccessfully tried to persuade Republican colleague Jim Bunning of Kentucky to drop his objection to passing a 30-day extension of unemployment benefits for jobless Americans.

In June 2018, he attempted to enter the Casa Padre processing facility in Brownsville, Texas, where children separated from their parents were being detained as a result of the Trump administration's "zero tolerance" policy.

In August 2018, Merkley was one of 17 senators to sign a letter spearheaded by Kamala Harris to United States Secretary of Homeland Security Kirstjen Nielsen demanding that the Trump administration take immediate action to reunite 539 migrant children with their families, citing each passing day of inaction as intensifying "trauma that this administration has needlessly caused for children and their families seeking humanitarian protection".

[39] In November 2018, Merkley was one of 11 senators to sign a letter to United States Secretary of Defense James Mattis about "the overt politicization of the military" with the Trump administration's deployment of 5,800 troops to the U.S.-Mexico border and requesting a briefing and written justification from the U.S. Northern Command for troop deployment, urging Mattis to "curb the unprecedented escalation of DOD involvement in immigration enforcement".

[40] In January 2019, Merkley was one of 20 senators to sponsor the Dreamer Confidentiality Act, a bill imposing a ban on the Department of Homeland Security (DHS) from passing information collected on DACA recipients to Immigration and Customs Enforcement (ICE), Customs and Border Protection (CBP), the Department of Justice, or any other law enforcement agency except in cases of fraudulent claims, national security issues, or non-immigration-related felonies.

[44] In November 2011, Merkley led an effort to urge President Obama to expedite transition of responsibility for military and security operations to the government of Afghanistan.

[45] The Senate passed an amendment to the defense authorization bill by voice vote that required Obama to deliver to Congress a timeline for an accelerated transition of all military and security operations to the Afghan government within 90 days of the law's enactment.

The senators requested the creation of "an independent Special Counsel to investigate collusion with the Russian government by General Flynn and other Trump campaign, transition and Administrative officials" in order to maintain "the confidence, credibility and impartiality of the Department of Justice".

[53] In December 2018, after United States Secretary of State Mike Pompeo announced the Trump administration was suspending its obligations in the Intermediate-Range Nuclear Forces Treaty in 60 days in the event that Russia continued to violate the treaty, Merkley was one of 26 senators to sign a letter expressing concern that the administration was "now abandoning generations of bipartisan U.S. leadership around the paired goals of reducing the global role and number of nuclear weapons and ensuring strategic stability with America's nuclear-armed adversaries" and calling on Trump to continue arms negotiations.

[56] In January 2024, Merkley voted for a resolution, proposed by Bernie Sanders, to apply the human rights provisions of the Foreign Assistance Act to U.S. aid to Israel's military.

[59][60] In March 2018, Merkley voted against tabling a resolution spearheaded by Bernie Sanders, Chris Murphy, and Mike Lee that would have required Trump to withdraw American troops either in or influencing Yemen within the next 30 days unless they were combating Al-Qaeda.

[68] A $2 billion trading loss at JPMorgan Chase & Co. in May 2012 prompted Merkley and Levin to push regulators to stiffen their draft language on the Volcker Rule provisions.

[28] Merkley also championed legislation that gives nursing mothers flexible break times and private space to pump breast milk at work.

"[76] In June 2019 Merkley and 14 other senators introduced the Affordable Medications Act, legislation intended to promote transparency by mandating that pharmaceutical companies disclose the amount of money going toward research and development in addition to both marketing and executives' salaries.

[78] As a member of the United States Senate Committee on Banking, Housing, and Urban Affairs, Merkley has contributed legislation toward fixing the subprime mortgage crisis.

[79][81] To speed the recovery of the housing market, Merkley supports aggressive efforts to create refinancing alternatives to costly and time-consuming foreclosures, including allowing federal bankruptcy judges to modify existing mortgages so they can keep their home under new terms.

"[88] In September 2018, Merkley was one of eight senators to sponsor the Climate Risk Disclosure Act, a bill described by cosponsor Elizabeth Warren as using "market forces to speed up the transition from fossil fuels to cleaner energy—reducing the odds of an environmental and financial disaster without spending a dime of taxpayer money.

[116] During the Postal Reform Act debate in the Senate in April 2012, Merkley led the effort to pass an amendment that would impose a one-year moratorium on the closure of most rural post offices.

With 11 other RFMA cosponsors, including fellow Oregon Senator Ron Wyden, Merkley released a video as part of the It Gets Better Project, the anti-bullying initiative aimed at inspiring at-risk LGBTQIA+ youth.

"[124] In October 2018, Merkley was one of 20 senators to sign a letter to Secretary of State Mike Pompeo urging him to reverse the rolling back of a policy that granted visas to same-sex partners of LGBTQIA+ diplomats who had unions that were not recognized by their home countries, writing that too many places around the world have seen LGBTQIA+ people "subjected to discrimination and unspeakable violence, and receive little or no protection from the law or local authorities" and that refusing to let LGBTQIA+ diplomats bring their partners to the U.S. would be equivalent to upholding "the discriminatory policies of many countries around the world.

They also asked why the LGBTQIA+ special envoy position had remained vacant and asserted that "preventing the official flying of rainbow flags and limiting public messages celebrating Pride Month signals to the international community that the United States is abandoning the advancement of LGBTQIA+ rights as a foreign policy priority.

"[128] In June 2019, Merkley and 18 other Democratic senators sent a letter to USDA Inspector General Phyllis K. Fong requesting that she investigate USDA instances of retaliation and political decision-making and asserting that not to conduct an investigation would mean these "actions could be perceived as a part of this administration’s broader pattern of not only discounting the value of federal employees, but suppressing, undermining, discounting, and wholesale ignoring scientific data produced by their own qualified scientists.

He said the bill "is a necessary step forward in clarifying trucking rules, to make sure businesses in every sector of Oregon’s agriculture industry have the same ability to deliver their products while they're still fresh.

The legislation also supported universal access to high-quality preschool programs for all 3- and 4-year-olds and changed child care workforce compensation and training to aid both teachers and caregivers.

"[132] In December 2016, Merkley was one of 17 senators to sign a letter to Trump asking him to fulfill a campaign pledge to bring down the cost of prescription drugs, stating their willingness "to advance measures to achieve this goal", and calling on Trump "to partner with Republicans and Democrats alike to take meaningful steps to address the high cost of prescription drugs through bold administrative and legislative actions.