Edwards disappeared on 1 February 1995, on the day when he and Bradfield were due to fly to the United States on a promotional tour of The Holy Bible. In the two weeks before his disappearance, Edwards withdrew £200 a day from his bank account, which totalled £2,800 by the day of the scheduled flight. It is not known if he intended to spend the cash during the U.S. tour or whether a part of it was to pay for a desk that he had ordered from a shop in Cardiff. There is no record of the desk having been paid for.
According to Emma Forrest, as quoted in A Version of Reason, "The night before he disappeared Edwards gave a friend a book called Novel with Cocaine, instructing her to read the introduction, which details the author staying in a mental asylum before vanishing." Whilst staying at the Embassy Hotel in Bayswater Road, London, according to Rob Jovanovic's biography, Edwards removed some books and videos from his bag. Among them was a copy of the play Equus. Edwards placed them in a box with a note that said "I love you", wrapped the box like a birthday present and decorated it with collages and literary quotations including a picture of a Germanic-looking house and Bugs Bunny. The package was addressed to Edwards' on/off girlfriend, Jo, whom he met some years prior, although they had split a few weeks earlier.
Edwards' sister, Rachel, contributing to an article about Edwards' final lyrics by Guy Mankowski, proposed that Sylvia Plath's poem 'Tulips' 'summed up everything he [Edwards] thought at the time he went'. She added, 'why do I know this? Because he told me, he kept a copy of it, and he asked for it to be read at his funeral'. Rachel Edwards said, 'his thoughts must have been dominated by this poem–the themes and messages.' The poem is generally considered to depict the tension between the speaker's desire for the simplicity of death and the tulip's encouragement towards life.
The next morning, Edwards collected his wallet, car keys, some Prozac and his passport. He reportedly checked out of the hotel at 7:00 a.m., leaving his toiletries, packed suitcase, and some of his Prozac. He then drove to his flat in Cardiff, leaving behind his passport, his Prozac and the Severn Bridge tollbooth receipt. In the two weeks that followed, Edwards was apparently spotted in the Newport passport office and at Newport bus station by a fan who was unaware that he was missing. The fan was reported to have discussed a mutual friend, Lori Fidler, before Edwards departed.
This timeline was turned on its head in 2018, due to the original assumption made over the toll booth ticket found from the Severn Bridge. It had been assumed that '2:55' on the ticket was 2:55 PM, but in 2018 the original software engineer of the bridge was located and he confirmed the software printed out the 24-hour clock, meaning Edwards passed this location at 2:55 AM. Therefore, the timeline of events and subsequent appeals for information were no longer valid.
On 7 February, a taxi driver from Newport supposedly picked up Edwards from the King's Hotel, and drove him around the valleys, including Edwards' hometown of Blackwood. The driver reported that the passenger had spoken in a Cockney accent, which occasionally slipped into a Welsh one, and that he had asked if he could lie down on the back seat. Eventually they reached Blackwood and the bus station, but the passenger reportedly said "this is not the place", and asked to be taken to Pontypool railway station. It was later ascertained, according to Jovanovic's account, that Pontypool did not have a telephone. The passenger got out at the Severn View service station near Aust, South Gloucestershire and paid the £68 fare in cash.
On 14 February, Edwards' Vauxhall Cavalier received a parking ticket at the Severn View service station, and on 17 February, the vehicle was reported as abandoned. Police discovered the battery to be dead, with evidence that the car had been lived in. The car also had photos he had taken of his family days prior. Due to the service station's proximity to the Severn Bridge, a known suicide site, it was widely believed that Edwards had jumped from the bridge. Many people who knew Edwards, however, have said that he was never the type to contemplate suicide and he himself was quoted in 1994 as saying, "In terms of the 'S' word, that does not enter my mind. And it never has done, in terms of an attempt. Because I am stronger than that. I might be a weak person, but I can take pain".
Since then, Edwards has reportedly been spotted in a market in Goa, India, and on the islands of Fuerteventura and Lanzarote. There have been other alleged sightings of Edwards, especially in the years immediately following his disappearance. However, none of these has proved conclusive, and none has been confirmed by investigators.
The investigation itself has received criticism. In his 1999 book Everything (A Book About Manic Street Preachers), Simon Price states that aspects of the investigation were "far from satisfactory". He asserts the police may not have taken Edwards' mental state into account when prioritising his disappearance, and also records Edwards' sister Rachel as having "hit out at police handling" after CCTV footage was analysed two years after Edwards vanished. Price records a member of the investigation team as stating "that the idea that you could identify somebody from that is arrant nonsense". While his family had the option of declaring him legally dead from 2002 onwards, they chose not to for many years, and his status remained open as a missing person until 23 November 2008, when he became officially "presumed dead".