The newspaper described Clinton as "one of the most tenacious politicians of her generation" and said she had displayed a command of policy and diplomatic nuance while building a reputation for grit and bipartisan cooperation.
"A lifetime’s commitment to solving problems in the real world qualifies Hillary Clinton for this job, and the country should put her to work," the Times said of the former secretary of state and U.S. senator from New York.
Clinton will face off against Trump on Monday night in the first of three presidential debates, with opinion polls showing her once sizable lead over the New York businessman narrowing amid continued public doubts about her trustworthiness.
The Times said Clinton's mistakes had distorted perceptions of her character, but praised her work restoring U.S. credibility in foreign affairs as secretary of state and on behalf of children, women and families throughout her career.
"Mrs. Clinton has shown herself to be a realist who believes America cannot simply withdraw behind oceans and walls, but must engage confidently in the world to protect its interests and be true to its values," the newspaper said.
It said Clinton's decision to use a private email server for government work as secretary of state deserved the scrutiny it has received in the campaign, but considered alongside the real challenges facing the United States it "looks like a matter for the help desk."
Viewed against those challenges, Trump "shrinks to his true small-screen, reality-show proportions," the Times said, promising another editorial on Monday explaining "why we believe Mr. Trump to be the worst nominee put forward by a major party in modern American history."
The endorsement from the Times editorial board is no surprise. The last Republican the Times backed for the White House was President Dwight Eisenhower in 1956. But several newspapers with more conservative editorial boards, including the Dallas Morning News and Cincinnati Enquirer, also have recently endorsed Clinton.
The Times said Clinton's best argument for the White House was her ability to rise to the challenges facing the country.
"The 2016 campaign has brought to the surface the despair and rage of poor and middle-class Americans" facing the burdens of recession, technological change, foreign competition and war, it said.
"Over 40 years in public life, Hillary Clinton has studied these forces and weighed responses to these problems. Our endorsement is rooted in respect for her intellect, experience, toughness and courage over a career of almost continuous public service, often as the first or only woman in the arena," the newspaper said.