This lyric was interpreted as a play on the title of Bowie's album Low (1977), which was inspired by the withdrawal symptoms he suffered while undergoing treatment for drug addiction.

Additionally, the choked and self-recriminating tone used in the lyrics "Time and again I tell myself I'll stay clean tonight" reinforces an autobiographical and retrospective interpretation.

At a certain point during the travel ('past one hundred thousand miles'), he claims that "he feels very still" and thinks that "my spaceship knows which way to go" and proceeds to say: "Tell my wife I love her very much."

"[3]In the promotional film from 1969, David Bowie plays as Major Tom, Ground Control (GC), and the Countdown Announcer.

The music video ends with Major Tom sitting in his "tin can", far above the world, with the two women by him in a ménage à trois formation.

The later verses seem to reflect more on Bowie's literal battle with addiction, specifically about wanting to stay clean but being stuck with a "valuable friend".

He has become a nursery rhyme in the minds of the public, with mothers warning against drug use by telling their children if they want: "...to get things done, you'd better not mess with Major Tom.

The same album also contains a cover of Legendary Stardust Cowboy's I Took a Trip on a Gemini Spaceship, again hinting a metaphoric connection between space journeys and drug use.

In the music video of Bowie's 2015 song "Blackstar" (on the album of the same name, released in 2016 two days prior to his death), a dead astronaut is depicted.

His jewel-encrusted skull is retrieved by an alien female who takes it back to what could be considered a cult which subsequently worships the relic.

Once in orbit Major Tom sees a shining spinning object in the distance and promptly loses contact with GC.

[17] Video game designer, director, and producer Hideo Kojima's admiration for Bowie inspired several elements in the Metal Gear series.

In season 3 episode 13 of Rugrats, "Destination Moon", Tommy says, "This is Major Tom, to ground control, requesting permission for lift off".

The song "Terrence Loves You" by Lana Del Rey, whose meaning is speculated by fans to be about David Bowie's brother Terry Burns, contains the lyrics "Ground Control to Major Tom / Can you hear me all night long?"

The song itself plays an important role in the Apple TV+ American science fiction television series Invasion, created by Simon Kinberg and David Weil.