"It's been joy to watch him spar with you," President Bush told the White House press corps in the briefing room Friday.
"I sadly accept his desire to leave the White House," Mr. Bush said.
Snow, who's battling cancer, had said recently he would leave before the end of Mr. Bush's presidency. The father of three children, Snow said he needs to make more than his White House salary of $168,000. He could earn far more money on the speechmaking circuit.
"He's smart. He's capable. He's witty. He's able to talk about issues in a way that the American people can understand," Mr. Bush said. "I don't know what he's going to do. I'm not sure he does yet, either.
"But whatever it is ... it's going to be two things - one, he'll battle cancer and win, and secondly, he'll be a solid contributor to society."
The 52-year-old Snow was a conservative pundit and syndicated talk-show host on Fox News Radio before he was named press secretary on April 26, 2006.
"This job has really been a dream for me, a real blast," Snow said at Friday's press briefing.
Snow has been undergoing chemotherapy after doctors discovered a recurrence of colon cancer in March. He said recent tests have revealed no new cancerous tumors.
Snow said his current plans are to give speeches, write, and otherwise stay visible in the political arena, as well as to speak about his cancer experience. "It's proved to be helpful to people," he said.
He is the latest in a string of White House officials to head for the exits.
Friday was the last day of work for political strategist Karl Rove. Others who have left since Democrats won control of Congress are counselor Dan Bartlett, chief White House attorney Harriet Miers, budget director Rob Portman, political director Sara Taylor, deputy national security adviser J.D. Crouch and Meghan O'Sullivan, another deputy national security adviser who worked on Iraq.
In 2005, Snow had his colon removed and underwent six months of chemotherapy after being diagnosed with cancer. This March, he underwent surgery to remove a growth in his abdominal area, near the site of the original colon cancer. Doctors determined it was a recurrence of his cancer.
He was out of work for five weeks, then returned and underwent chemotherapy, treatments that only recently concluded and have left him thinner, grayer and with less hair.
Snow earned his stripes within the White House for his striking popularity around the country, relentlessly good-natured and bright tone, and smooth, snappy repartee with the media during briefings. Reporters, though, grumbled that an emphasis on showmanship too often took precedence over rhetorical precision and careful preparation.
Some senior White House aides referred to his briefings as "The Tony Snow Show."
Snow was President Bush's third chief spokesman in just over six years that have been marked by increasingly tense relations between the White House and the reporters who cover it.
Snow had little experience as a press secretary before joining the White House team. He worked in the White House under Mr. Bush's father as a speechwriting director and spokesman for regional issues. As a pundit, he had been sharply critical of Mr. Bush at times.
He held several print journalism positions, mostly working for newspaper opinion pages, and was most recently the host of the "Tony Snow Show" on Fox News Radio and "Weekend Live with Tony Snow" on the Fox News Channel.
Perino, 35, has been Snow's principal deputy, filling in for him when he was away after surgery and at other times.
On taking over the job, Perino remarked, "He leaves very big shoes to fill, and I'm only a size 6."
Before joining the press office, she worked as associate director of communications at the White House Council on Environmental Quality.