Dewey Bunnell, the song's vocalist and writer, has said that the lyric "alligator lizards in the air" in the song is a reference to the shapes of clouds in the sky he saw in 1963 while his family was driving down the coast from Vandenberg Air Force Base near Lompoc, California where they had a flat tire. While his father changed the tire, he and his brother stood by the side of the road and watched the clouds and saw a road sign for "Ventura".
In the booklet for the boxed-set, Highway, he states that the song "reminds me of the time I lived in Omaha as a kid and how we'd walk through cornfields and chew on pieces of grass. There were cold winters, and I had images of going to California. So I think in the song I'm talking to myself, frankly: 'How long you gonna stay here, Joe?' I really believe that 'Ventura Highway' has the most lasting power of all my songs. It's not just the words — the song and the track have a certain fresh, vibrant, optimistic quality that I can still respond to". The song has a "Go West, young man" motif in the structure of a conversation between an old man named Joe and a young and hopeful kid. Joe was modeled after a "grumpy" old man he had met while his dad was stationed in Biloxi, Mississippi at Keesler Air Force Base.
"That's Gerry and Dan doing a harmony on two guitars on the intro. I remember us sitting in a hotel room, and I was playing the chords, and Gerry got that guitar line, and he and Dan worked out that harmony part. That's really the hook of the song".
The song also contains the phrase "purple rain," later the title of a 1984 song, album, and film (and the tour that supported both the album and film), for the artist Prince. Although it is not known if there is actually any connection, both Mikel Toombs of The San Diego Union and Bob Kostanczuk of the Post-Tribune, have written that Prince got the title directly from "Ventura Highway". Asked to explain the phrase "purple rain" in "Ventura Highway", composer Gerry Beckley has responded: "You got me" [i.e. he can't].
The song's opening guitar riff and musical hook is sampled throughout Janet Jackson's 2001 song "Someone to Call My Lover" by the production team of Jimmy Jam and Terry Lewis who were influenced by America and "Ventura Highway" listening to KDWB 63 AM (Top 40) growing up in Minneapolis, Minnesota (along with their close friend, musician Prince). Bunnell said the use of the sample from Ventura Highway and the production by Jimmy Jam, Terry Lewis and Janet Jackson boosted sales for America.
The song won many fans, including the pro-wrestler-turned-politician, Jesse Ventura: "We went and played at Governor Jesse Ventura's inaugural out in Minneapolis. He asked us to — his wife is a horse lady, and she'd always loved A Horse With No Name, and he had adopted this name Ventura. So when he put together his cast of characters for his big inaugural celebration, he wanted us to come and play two songs, which we did".