Director Cameron Crowe couldn't find the love song he wanted until he heard Peter Gabriel's "In Your Eyes". Gabriel asked to see part of the movie. Crowe had the production company send him an unfinished cut. Gabriel responded by saying he would let them use the song, as he liked the film. He was, however, wary about the part where the lead character overdosed at the end. It was then that Crowe realized that Gabriel had been sent a copy of Wired (1989) instead.
Producer James L. Brooks said what inspired this movie was an incident where Brooks saw a man walking with his daughter. He saw them and wondered what would happen if the father committed a crime. Those thoughts were used to create the story.
The exchange between Lloyd and Jason about an album titled "Hey Soul Classics" is a reference to a TV commercial that aired frequently in the 1980s. "Hey Love" was a compilation of 1970s R&B songs that was sold on TV. A line from the commercial, "No, my brother. You've got to buy your own," became a catchphrase at the time.
The Smithereens were commissioned by Cameron Crowe to write the theme song for the movie, and they came up with "A Girl Like You". Crowe thought that the lyrics were too leading (they outline the entire plot), so he rejected it in favor of Peter Gabriel's "In Your Eyes". "A Girl Like You" went on to be included in The Smithereens' next album, "11", and in the movie Backdraft (1991) by Ron Howard.
Cameron Crowe said in an interview, "Few people know this, but Stone Gossard is actually in Say Anything... (1989) He plays a cab driver, and Ione Skye looks at him and kind of flirts with him a little bit as they're stuck in traffic on her way to graduation."
Lloyd and Diane's school appears to be based on The Lakeside School, which is a very prestigious Seattle private school. In the movie, the school is called "Lakewood" (and has a rooster mascot, rather than a lion), but in Lloyd's first phone conversation with Diane, John Cusack mentions that at his annual party, Lloyd "dresses up as the Lakeside rooster."
Lloyd makes several references in the movie to "Bell Square" mall, short for Bellevue Square (located in Bellevue, Washington). When Lloyd is driving in the rain and sees the mall, he is actually driving by Westlake Center (located in downtown Seattle).
Ione Skye has admitted on the film's audio commentary that there was definitely off-screen chemistry between her and John Cusack during filming, and that had they not been involved with other people at that time, they probably would have gone home together the day they shot the scene where Lloyd teaches Diane to drive a stick shift.