More than 200 people who previously worked for President George W. Bush and Senators Mitt Romney and John McCain have signed a letter endorsing Vice President Kamala Harris.

Many of the more prominent signatories, including a chief of staff, a legislative director and a deputy campaign manager for Mr. McCain, had signed a letter supporting President Biden in the 2020 election. Others work for organizations like The Bulwark and the Lincoln Project that oppose former President Donald J. Trump’s leadership of the Republican Party.

But the former Republican officials’ renewed support of the Democratic ticket reflects how Mr. Trump has transformed the Republican Party under his leadership, as well as deep and persistent opposition to his candidacy from those who served Republican presidential candidates.

Mr. Romney, Mr. Bush and other high-profile Republicans skipped the Republican nominating convention last month, while the Harris campaign made significant efforts to highlight the support of anti-Trump Republicans — as well as former members of Mr. Trump’s staff who no longer support him — with speaking slots at the Democratic convention last week.

“We have plenty of honest, ideological disagreements with Vice President Harris and Gov. Walz,” the letter said. “That’s to be expected. The alternative, however, is simply untenable.”

The signatories include Mark Salter, a former chief of staff for Mr. McCain; Joe Donoghue, the senator’s former legislative director; Reed Galen, his deputy campaign manager and a co-founder of the Lincoln Project; Mike Murphy, a former McCain campaign strategist; Jean Becker, a chief of staff for George H.W. Bush; and Jim Swift, a senior editor of The Bulwark.