The CBS late-night host, building on Thursday's startling confessional, vowed to repair his relationship with his wife, Regina Lasko, whom he married in March after a years-long courtship.
"Let me tell you folks, I got my work cut out for me," he said ruefully.
As Letterman faced Monday's show, and the shows that will come after, it was clear that how he deals with his messy situation could prove to be a defining chapter in his long TV career. And, ironically, it could clinch his recent ratings victory in late-night TV.
His dilemma was Topic A on the show as he mixed wisecracks with contrition in a virtuoso balancing act. Noting the cool fall weather, he reported, "It's chilly outside my house; chilly INSIDE my house."
Then he cautioned the audience, "This is only Phase 1 of the scandal. Phase 2: Next week I go on 'Oprah' and sob."
A bit later, guest Steve Martin gave Letterman his kidding consolation: "It proves that you're a human being. And we weren't really that sure before."
Martin Short, making an unannounced appearance, playfully plopped himself in Martin's lap.
"You spend one more minute on his lap, you're gonna get blackmailed," Letterman quipped.
Monday's show was the first Letterman had taped since Thursday, when he disclosed that he had had sexual relationships with women who worked for him and said that he had been the victim of a $2 million blackmail threat.
During the hour, he also apologized to his staff, which, he said, had been subjected to "being browbeaten and humiliated" by reporters since his revelations.
"My thanks to the staff for, once again, putting up with something stupid I've gotten myself involved in," he said.
Letterman, 62, began dating Lasko in 1986, and they have a son, Harry, who was born in November 2003. All the affairs took place before Letterman's marriage, said Tom Keaney, spokesman for Letterman's production company, Worldwide Pants.
Letterman arrived on stage Monday to applause and cheers from his studio audience. After drinking it in, he grinned sheepishly and inquired, with a mock stammer, "Did your, did your weekend just fly by?"
After pausing for the audience's sympathetic laughter, he went on: "I mean, I'll be honest with you folks _ right now, I would give anything to be hiking on the Appalachian Trail."
"I got into the car this morning," he added, "and the navigation lady wasn't speaking to me. Ouch."
In a more somber display, Letterman voiced his mea culpas. Regarding his wife, he said that, "if you hurt a person and it's your responsibility, you try to fix it."
Letterman has offered no specifics about how many women he had sex with.
But the CBS producer accused of blackmailing Letterman used pages from a former assistant's diary that described an affair with the "Late Show" host, a law enforcement official said Monday. The ex-assistant, Stephanie Birkitt, went to live with CBS News producer Robert Halderman, who found her diary describing her relationship with Letterman and used it to help blackmail him, the law enforcement official said Monday on the condition of anonymity because the investigation was ongoing.
Halderman, a producer for the true-crime show "48 Hours Mystery," pleaded not guilty last week to extortion charges.
The flood of attention on Letterman was inevitable, and the way he initially dealt with this maelstrom recalled an embarrassing dilemma for another star in 1995.
For a celebrity the caliber of Hugh Grant, publicity _ including speculation of career suicide _ was unavoidable when he was arrested with a prostitute on Hollywood's Sunset Strip 14 ears ago. But then he retreated to NBC's "The Tonight Show" to try to explain.
Host Jay Leno wasted no time before asking an instant classic of a question: "What the hell were you thinking?!"
Grant's appearance provided him with some needed image rehab. It also vaulted ratings runner-up "Tonight" past Letterman's "Late Show," a leadership position Leno held through his retirement from late night earlier this year.
Since then, Letterman has reclaimed a ratings edge over new "Tonight" host Conan O'Brien.
And now he may have truly sealed the deal. Beloved by viewers and critics for decades, he has abruptly freshened the enduring Letterman brand and demonstrated he still has the ability to surprise even fans who thought they knew him well.
Indeed, a legendary late-night host has nothing but praise for Letterman's skill at crisis management.
But it isn't the first time Letterman has shown finesse in managing a firestorm.
In June, he had a run-in with former Alaska Gov. Sarah Palin over jokes made at the expense of her teenage daughter. He emerged from a tumultuous few days of protests and demands for his dismissal with a ratings jolt. And thanks to the dumb-luck timing of the flap, he also handily upstaged his much-hyped NBC rival just as O'Brien was taking over as "Tonight" host.
Letterman apologized to Palin and her family in what became another one of his memorable performances. But he has never stopped making jokes at Palin's expense _ including yet another apology to her on Monday's show, just for good measure.
Associated Press writer Jake Coyle contributed to this report.