Pang was asked to help Lennon and his wife Yoko Ono with their avant-garde film projects, Up Your Legs Forever and Fly, in December 1970. Pang was then asked to be Lennon and Ono's secretary and factotum/gofer in New York and England, which led to a permanent position as their personal assistant when the Lennons moved from London to New York in 1971. Pang coordinated an art exhibition in Syracuse, New York, on October 9, 1971, for Ono's This Is Not Here art show at the Everson Museum. Ono's show coincided with Lennon's 31st birthday, and a party was held at the Hotel Syracuse, which was attended by Ringo Starr, Phil Spector, and Elliot Mintz, among others.
Lennon called his 18-month relationship with Pang his "Lost Weekend", a reference to the film and novel of the same name.
In summer 1973, Pang was working on the recording of Lennon's Mind Games album. Lennon and Ono were having marital problems and decided to separate, and Ono suggested to Pang that she become Lennon's companion. Ono explained that she and Lennon were not getting along, had been arguing and were growing apart, and said that Lennon would start seeing other women. She pointed out that Lennon had said he found Pang sexually attractive. Pang replied that she could never start a relationship with Lennon as he was her employer and married. Ono ignored Pang's protests and said that she would arrange everything. In October 1973, Lennon and Pang left New York for Los Angeles to promote Mind Games, and decided to stay for a while, living at the homes of friends.
In March 1974, Lennon began producing Harry Nilsson's Pussy Cats album, thus named to counter the "bad boy" image the pair had earned in the media with two drinking incidents at The Troubadour: the first when Lennon placed a Kotex on his forehead and scuffled with a waitress and, two weeks later, when Lennon and Nilsson were ejected from the same club after heckling the Smothers Brothers. Lennon thought it would be a good idea for the musicians to live under one roof to ensure they would get to the studio on time, so Pang rented a beach house in Santa Monica, for her, Lennon, Nilsson, Ringo Starr and Keith Moon to live in. At this time, Pang encouraged Lennon to reach out to family and friends. He and Paul McCartney mended fences and played together for the first and only time after the breakup of The Beatles (see A Toot and a Snore in '74). Pang also arranged for Julian Lennon to visit his father for the first time in four years.
Julian began to see his father more regularly. Lennon bought Julian a Gibson Les Paul guitar and a drum machine for Christmas in 1973, and encouraged Julian's interest in music by showing him some chords. “Dad and I got on a great deal better then,” recalls Julian. “We had a lot of fun, laughed a lot and had a great time in general when he was with May Pang. My memories of that time with Dad and May are very clear—they were the happiest time I can remember with them.”
In June 1974, Lennon and Pang returned to live in New York City. Lennon stopped drinking and concentrated on recording. As Lennon had previously had cats in Liverpool—while living at his aunt Mimi's house—he and Pang adopted two cats which they named Major and Minor. In the early summer, while Lennon was working on his Walls and Bridges album, the couple moved into a penthouse apartment at 434 East 52nd Street, where Lennon and Pang claim to have seen a UFO on August 23, 1974, from their terrace, which had a panoramic view of east New York. To gain access to the deck Lennon and Pang had to climb out of their kitchen window. On the night in question, a naked Lennon excitedly called Pang to join him on outside and they both watched a circular object silently floating less than 100 feet away. Lennon called Bob Gruen—Lennon's "official" photographer—and told him what had happened. Gruen suggested Lennon should call the police, but Lennon laughed it off, saying, "I’m not going to call up the newspaper and say, 'This is John Lennon and I saw a flying saucer last night'". Gruen called the local police precinct which confirmed that three other people had reported a sighting, and the Daily News said that five people had reported a sighting in the same area of New York where Lennon and Pang lived.
Walls and Bridges rose to the top spot on the album charts. Lennon achieved his only number one solo single in his lifetime with "Whatever Gets You Thru the Night". Pang's is the voice whispering Lennon's name on "#9 Dream". Another song, "Surprise, Surprise (Sweet Bird of Paradox)", was written about her. Julian played drums on the album's last track, "Ya Ya". While recording Walls and Bridges, Al Coury, vice president of promotion for Capitol Records, got possession of the chaotic Spector session tapes and brought them to New York. Lennon would complete his oldies album, which would be called Rock 'n' Roll, with the same musicians he used on Walls and Bridges. Pang received an RIAA gold record award for her work on Walls and Bridges and continued her work as production coordinator of Lennon's Rock 'n' Roll album, where she was credited as "Mother Superior". Pang also worked on albums by Nilsson, Starr, Elton John and David Bowie.
While visiting Mick Jagger in Montauk, New York (part of The Hamptons area), Lennon and Pang saw a Scottish-style cottage that was for sale—which was close to the Montauk Point Lighthouse. Lennon asked a real estate broker to put in an offer for it in February 1975. Lennon and Pang were also planning on visiting Paul and Linda McCartney in New Orleans in February 1975, where Wings were recording the Venus and Mars album, but Lennon reconciled with Ono the day before the planned visit, after Ono said she had a new cure for Lennon's smoking habit.
Although Lennon would lament this period, he did not do so in private. Journalist Larry Kane, who befriended Lennon in 1964, wrote a comprehensive biography of Lennon which detailed the "Lost Weekend" period. In the interview with Kane, Lennon explained his feelings about his time with Pang: "You know Larry, I may have been the happiest I've ever been... I loved this woman (Pang), I made some beautiful music and I got so fucked up with booze and shit and whatever."
After Lennon went back to Ono, Pang started working for United Artists Records and Island Records as a PR manager, working on albums by Bob Marley and Robert Palmer.
Pang published her memoir, Loving John, in 1983. It was later updated and renamed, John Lennon: The Lost Weekend. The original 500-page Loving John book focused more on Pang's role on Lennon's albums and sessions. It was edited down to 300 pages, concentrating mostly on the sensational aspects of their relationship. It also included postcards that Lennon had written to Pang during his travels throughout the world in the late 70s. Pang claims that she and Lennon remained lovers until 1977, and stayed in contact until his death.
Pang's book of photographs, Instamatic Karma, was published in 2008. Besides the candid personal portraits, the book contains some historically important photographs, such as Lennon signing the official dissolution of The Beatles partnership, and the last known photograph of Lennon and Paul McCartney together. Cynthia Lennon also provided a back cover endorsement, acknowledging Pang's role in reuniting Lennon with his estranged first son, Julian.