The game was originally going to be called "What If".

When searching Victoria's room, if the player examines the TV, Max will refer to Final Fantasy: Spirits Within as one of the greatest sci-fi movies ever made. The Final Fantasy games are created by Square Enix, the same company that published Life is Strange

In the girls dorm, Room 217's board reads "REDRUM", a clear reference to The Shining.

According to Michel Koch, co-director of Life Is Strange, the character Warren Graham was inspired by Xander from the television show "Buffy the Vampire Slayer". In an interview with Vice, he states "I'm a huge fan of Buffy the Vampire Slayer. This is why I like looking at archetypes, like, uh Xander. He has this kind of awkwardness in him and is always saying the wrong things, but he's a good guy!"

According to Jean-Maxime Moris, Creative Director at Dontnod, Max Caulfield's surname is a reference to the character Holden Caulfield, the protagonist of the J. D. Salinger novel "The Catcher in the Rye". The two works share similar themes, such as the difficulties in making the transition from adolescence to adulthood. Like Max, Holden is a student at an exclusive boarding school, and both characters have similar personality traits such as the urge to preserve innocence. There are several other references to the book throughout the game.

Brooke's hoodie in episode 1 is a reference to Star Wars, and is designed to look like three lightsabers. This reference was later confirmed on Star Wars Day (May 4th) by the developers on Twitter.

The 'Eye of Providence' appears frequently around Blackwell Academy, including the girls bathroom, the Prescott Dormitory, and the entrance of the parking lot.

The 'Eye of Providence' is an ancient symbol that originally represented the all-seeing eye of God. It can be found in numerous settings both secular and religious, including the official seals of various cities, the stained glass windows of churches, and the Declaration of the Rights of Man and of the Citizen. In popular culture, however, it has come to represent a variety of conspiracy theories, usually involving Freemasonry or the Illuminati.

The poster in Max's room for "the WINGER and the COW" is clearly based on the cover of the novel "The Catcher in the Rye" by J.D. Salinger.

In Chloe's room, there is graffiti on the wall that says "everybody lies no exceptions". This is a line from the animated MTV series "Daria", based around cynical high-school student Daria Morgendorffer.

When Max waters Lisa the Plant at the beginning of episode 2, she says, "Drink up... it's got electrolytes". This quote is a reference to the film Idiocracy, where a sports drink is used to water crops.

In episode 4, if Max inspects the red hunting cap in the principal's office she will remark that "only a total phony would wear a crappy hat like that." This a reference to Holden Caulfield from the novel The Catcher in the Rye, who wears an identical red hunting cap and frequently calls others "phonies".

One of the posters around Blackwell Academy advertises a video game club called "Gamer Guyz" and lists their contact email as "JRomero". This is likely a reference to famous game developer John Romero, best known as a co-founder of id Software, and responsible for many of their most well known games, including Wolfenstein 3D, Hexen, Doom, and Quake.

Inside of the girl's dormitory is a poster advertising a "Geek Grrls" Book Club. It mentions several well-known fantasy and science fiction authors, such as Ursula K. LeGuin, Robin Hobb, Neil Gaiman, Piers Anthony, Terry Brooks, David Calvo, and Marion Zimmer Bradley.

In the parking lot of Blackwell Academy, there are references to several television series hidden on some of the license plates:

• "QNT MLP" - Quantum Leap
• "BRDCHRCH" - Broadchurch
• "TWN PKS" - Twin Peaks
• "B R K B D" - Breaking Bad
• "SXFTNDR" - Six Feet Under
• "THPRCTC" - The Practice
• "PRK SN RC" - Parks and Recreation
• "TH WR" - The Wire
• "CRNVL" - Carnivále
• "THSPRNS" - The Sopranos
• "TWLGHTZN" - The Twilight Zone
• "THXFLS" - The X-Files
• "BFFVMPRSLR" - Buffy the Vampire Slayer

A sticker of "LOL Guy" can be seen on the rear view mirror of Chloe Price's truck.

The car in the Madsen's garage has a license plate that reads 'TRDTCTV'. This is likely a reference to the television show "True Detective".

Warren's t-shirt in episode 2 shows a cartoon drawing of a box with a "meow!" speech bubble above it, referencing the Schrodinger's cat thought experiment.

On the mirror of the Two Whales Diner's bathroom, the phrase "Fire Walk With Me" is written on the mirror. This is a reference to the film Fire Walk With Me, a prequel to the events of the television show Twin Peaks. Much of the game's themes were inspired by the show, whose premise also involves the disappearance of a well-liked teenage girl.

There is a photo of Joyce with the real life novelist Ken Kesey hanging over the jukebox in the Two Whales Diner. Ken Kesey spent much of his life in Oregon, where the game takes place.

At the beginning of the first episode, Mr. Jefferson utters "Bueller" when no one volunteers to answer one of his questions. This is a quote from the movie "Ferris Bueller's Day Off", where a teacher taking attendance continues to recite Ferris' name several times without response when he's absent.