The Health and Human Services secretary became the first member of the president's Cabinet to be pushed out in a turbulent young administration that has seen several high-ranking White House aides ousted. A former GOP congressman from the Atlanta suburbs, Price served less than eight months.
Publicly, Trump had said he was "not happy" with Price for repeatedly using private charter aircraft for official trips on the taxpayer's dime, when cheaper commercial flights would have done in many cases.
Privately, Trump has been telling associates in recent days that his health chief had become a distraction. Trump felt that Price was overshadowing his tax overhaul agenda and undermining his campaign promise to "drain the swamp" of corruption, according to three people familiar with the discussions who spoke on condition of anonymity.
On Friday the president called Price a "very fine person," but added, "I certainly don't like the optics." Price said in his resignation letter that he regretted that "recent events have created a distraction."
The flap prompted scrutiny of other Cabinet members' travel, as the House Oversight and Government Reform committee launched a governmentwide investigation of top political appointees. Other department heads have been scrambling to explain their own travel.
Interior Secretary Ryan Zinke faced scrutiny over three charter flights while in office, including a $12,375 late-night trip from Las Vegas to his home state of Montana in June. On Friday, he dismissed the controversy over charter flights as "a little BS over travel," but he said taxpayers do have the right to know official travel costs.
Price's repayment of $51,887.31 for his own travel costs did not placate the White House. The total travel cost, including the secretary's entourage, was unclear. It could amount to several hundred thousand dollars.
Following Price's resignation, White House budget director Mick Mulvaney informed Cabinet secretaries and agency heads in a memo that approval from chief of staff John Kelly will be required for any travel on government-owned, rented, leased or chartered aircraft.
An orthopedic surgeon turned politician, Price rose to Budget Committee chairman in the House, where he was known as a fiscal conservative. When Price joined the administration, Trump touted him as a conservative policy expert who could write a new health care bill to replace the Obama-era Affordable Care Act.
But Price became more of a supporting player in the GOP's futile health care campaign, while Vice President Mike Pence took the lead, particularly with the Senate. The perception of Price jetting around while GOP lawmakers labored to repeal "Obamacare" -including a three-nation trip in May to Africa and Europe- raised eyebrows on Capitol Hill. Price flew on military aircraft overseas.
Although much of Trump's ire over the health care failure has been aimed at the Republican-controlled Congress, associates of the president said he also assigns some blame to Price, who he believes did not do a good job of selling the GOP plan.
But House Speaker Paul Ryan, R-Wis., said Friday that Price had worked hard to help that chamber pass its plan before the GOP effort reached an impasse in the Senate. "I will always be grateful for Tom's service to this country," he said.
Democrats were glad to see Price go. Some urged Trump to appoint an HHS secretary who would reach out to them.
"I hope President Trump learns from this mistake, and looks to appoint someone who can work in a bipartisan way to strengthen health care for all Americans," said Rep. Frank Pallone, D-N.J.
A Pence protege, Seema Verma, has been mentioned as a possible successor to Price. Verma already leads the Centers for Medicare and Medicaid Services, which runs health insurance programs that cover more than 130 million Americans.
Another possible HHS candidate: FDA Commissioner Scott Gottlieb, who won some bipartisan support in his confirmation and is well known in policy, government and industry circles.
Trump named Don J. Wright, a deputy assistant secretary of health, to serve as acting secretary.
Price, 62, was seen in Congress as a foe of wasteful spending. As HHS secretary, he led a $1 trillion department whose future is the key to managing mounting federal budgetary deficits. As secretary, Price criticized the Medicaid health program for low-income people, saying it doesn't deliver results commensurate with the hundreds of billions of dollars taxpayers spend on it. As a congressman, he favored Medicare privatization.
But Price's image as a budget hawk took a hit when reports of his official travel started bubbling up. Price used private charter flights on 10 trips with multiple segments, when in many cases cheaper commercial flights were available. His charter travel was first reported by the news site Politico.
On a trip in June to Nashville, Tennessee, Price also had lunch with his son, who lives in that city, according to Politico. Another trip was from Dulles International Airport in the Washington suburbs to Philadelphia International Airport, a distance of 135 miles.
The reports triggered a review by the HHS inspector general's office, which is looking into whether Price's travel violated federal travel regulations. Those rules generally require officials to minimize costs.
The controversy over Price was a catalyst for Congress launching a bipartisan probe of travel by political appointees across the administration. The House oversight committee has requested travel records from the White House and 24 federal departments and agencies.
Initially, Price's office said the secretary's busy scheduled forced him to use charters from time to time.
But later Price's response changed, and he said he'd heard the criticism and concern, and taken it to heart.
WATCH: Notable firings and resignations under the Trump administration