O'Connor, 75, said she expects to leave before the start of the court's next term in October, or whenever the Senate confirms her successor. There was no immediate word from the White House on who might be nominated to replace O'Connor.
It's been 11 years since the last opening on the court, one of the longest uninterrupted stretches in history. O'Connor's decision gives President Bush his first opportunity to appoint a justice.
"This is to inform you of my decision to retire from my position as an associate justice of the Supreme Court of the United States, effective upon the nomination and confirmation of my successor," she said in a one-paragraph letter to Bush. "It has been a great privilege indeed to have served as a member of the court for 24 terms. I will leave it with enormous respect for the integrity of the court and its role under our constitutional structure."
O'Connor's retirement came amid speculation that the aging court would soon have a vacancy. But speculation has most recently focused on Chief Justice William H. Rehnquist, 80, and suffering from thyroid cancer. Rehnquist has offered no public clue as to his plans.
The White House has refused to comment on any possible nominees, or whether Bush would name a woman to succeed O'Connor. Her departure leaves Justice Ruth Bader Ginsburg as the only other woman among the current justices.
Possible replacements include Attorney General Alberto R. Gonzales and federal courts of appeals judges J. Michael Luttig, John Roberts, Samuel A. Alito Jr., Michael McConnell, Emilio Garza and James Harvie Wilkinson III. Others mentioned are former Solicitor General Theodore Olson, lawyer Miguel Estrada and former deputy attorney general Larry Thompson, but Bush's pick could be a surprise choice not well known in legal circles.
Another prospective candidate is Edith Hollan Jones, a judge on the 5th U.S. Circuit Court of Appeals who was also considered for a Supreme Court vacancy by President Bush's father.
O'Connor's appointment in 1981 by President Ronald Reagan, quickly confirmed by the Senate, ended 191 years of male exclusivity on the high court.
She wasted little time building a reputation as a hard-working moderate conservative who emerged as a crucial power broker on the nine-member court.
O'Connor often lines up with the court's conservative bloc, as she did in 2000 when the court voted to stop Florida presidential ballot recounts sought by Al Gore, and effectively called the election for Bush.
As a "swing voter," however, O'Connor sometimes votes with more liberal colleagues.
Perhaps the best example of her influence is the court's evolving stance on abortion. She distanced herself both from her three most conservative colleagues, who say there is no constitutional underpinning for a right to abortion, and from more liberal justices for whom the right is a given.
O'Connor initially balked at letting states outlaw most abortions, refusing in 1989 to join four other justices who were ready to reverse the landmark 1973 decision that said women have a constitutional right to abortion.
Then in 1992, she helped forge and lead a five-justice majority that reaffirmed the core holding of the 1973 ruling. Subsequent appointments secured the abortion right. Commentators called O'Connor the nation's most powerful woman, but O'Connor poo-poohed the thought.
"I don't think it's accurate," she said in an Associated Press interview.
O'Connor in late 1988 was diagnosed as having breast cancer, and she underwent a mastectomy. She missed just two weeks of work. That same year, she had her appendix removed.
For years, O'Connor had an involuntary nodding of her head, but said she never had it diagnosed. The movement, while not constant, was an up-and-down motion similar to that made by someone nodding in the affirmative.
O'Connor remained the court's only woman until 1993 when, much to O'Connor's delight and relief, President Bill Clinton appointed Ginsburg.
The enormity of the reaction to O'Connor's appointment had surprised her. She received more than 60,000 letters in her first year, more than any one member in the court's history.
"I had no idea when I was appointed how much it would mean to many people around the country," she once said. "It affected them in a very personal way. People saw it as a signal that there are virtually unlimited opportunities for women. It's important to parents for their daughters, and to daughters for themselves."
At times, the constant publicity was almost unbearable. "I had never expected or aspired to be a Supreme Court justice. My first year on the court made me long at times for obscurity," she once said.
On the court, O'Connor generally favored states in disputes with the federal government and for enhanced police powers challenged as violative of asserted individual rights.
In 1985, she wrote for the court as it ruled that the confession of a criminal suspect first warned about his rights may be used as trial evidence even if police violated a suspect's rights in obtaining an earlier confession.
O'Connor wrote the 1989 decision that struck down as an unconstitutional form of affirmative action a minority set-aside program for construction projects in Richmond, Va.
In 1991, she led the court as it ruled in its first-ever decision on rape-shield laws that states may under some circumstances bar evidence that a defendant and his alleged victim previously had consensual sex.
"When (someone) lights a fire, we invariably are asked to attend to the blaze. We may arrive at the scene a few years later," she said.
O'Connor was 51 when she joined the court to replace the retired Potter Stewart. A virtual unknown on the national scene until her appointment, she had served as an Arizona state judge, and before that as a member of her state's Legislature.
A fourth-generation Arizonan, she had grown up on a sprawling family ranch.
The woman who climbed higher in the legal profession than had any other member of her sex did not begin her career auspiciously. As a top-ranked graduate of Stanford's prestigious law school, class of 1952, O'Connor discovered that most large law firms did not hire women.
One offered her a job as a secretary. Perhaps it was that early experience that shaped O'Connor's professional tenacity. She once recalled a comment by an Arizona colleague: "With Sandra O'Connor, there ain't no Miller time."
"I think that's true," confessed the justice whose work week most often extended beyond 60 hours.
But she played tennis and golf well, danced expertly with her husband, John, and made frequent appearances on the Washington party circuit.
O'Connor was embarrassed in 1989 after conservative Republicans in Arizona used a letter she had sent to support their claim that the United States is a "Christian nation."
The 1988 letter, which prompted some harsh criticism of O'Connor by legal scholars, cited three Supreme Court rulings in which the nation's Christian heritage was discussed.
O'Connor said she regretted the letter's use in a political debate. "It was not my intention to express a personal view on the subject of the inquiry," she said.
O'Connor's name was linked in 1985 with that of Washington Redskins football star John Riggins when at a formal dinner he was heard to tell the justice sharing his table, "Loosen up, Sandy baby."
Shortly thereafter, the women who participated with O'Connor at an 8 a.m. daily exercise class presented her with a tee-shirt that proclaimed: "Loosen up at the Supreme Court."
The O'Connors have three sons, Scott, Brian and Jay.