"[Courteney] knows she's not f***ing me, and she's like, 'Listen, I want you to be able to do whatever you have to do,'" he said. Arquette admitted to sleeping with Waltz, whom he called "the girl in the paper," "once ... maybe twice."
Arquette added that Cox, 46, wanted him to grow up.
"She says that to me: 'I don't want to be your mother anymore,'" he said. "I appreciated that. I respected that. I've been going to therapy. I'm trying to grow up. I'm trying to be true to myself. Trying to figure out myself and my world, as is she."
He also revealed how he broke the news to their 6-year-old daughter, Coco.
"We went to a beach and had a picnic," Arquette said. "[I] explained to her that we're grown-ups, and a lot of the time when grown-ups are growing up, they need to figure out their lives."
Arquette hopes the separation won't end in divorce.
"We're still working it out," he told Stern. "We're being very sweet and kind to each other."
But with both parties free to move on -- Arquette told Stern that he and Cox agreed they could be intimate with other people during their separation -- reconciliation may be less than likely.
"You've got two very different kinds of people who have probably not seen eye to eye for years. After the infatuation wore off, they probably realized that," said Helen Fisher, chief scientific adviser to Chemistry.com and author of the relationship analysis tome "Why Him, Why Her?"
"She's what I call the director, he's more of a negotiator," Fisher said. "I'm not surprised that she's being practical about this, and he's being syrupy, because the director type tends to be decisive and tough-minded. She probably found that he was sleeping with someone else and she's not willing to negotiate that. She would probably rather find someone else."
Cox has yet to offer details as candid as Arquette's. According to RadarOnline.com, after their separation, she may be engaging in a more-than-professional relationship with her "Cougar Town" co-star, Brian Van Holt, 40.
Arquette's current fixation appears to be Waltz, a 28-year-old lithe brunette who could serve as Megan Fox's stunt double (and for that matter, looks not unlike a younger version of Cox). Waltz has been romantically linked to a number of celebrities, including Ryan Seacrest, Chris Pine, Jesse McCartney and Paris Hilton's ex-boyfriend, Doug Reinhardt. She's also infamous for reportedly punching Lindsay Lohan at a Hollywood nightclub in July.