A joke existed in early versions of the game when Guybrush would look at the statue in the voodoo shop. When the player would use the "Look At" command on the statue, Guybrush would respond, "Looks like an emaciated Charles Atlas." LucasArts received a cease and desist letter because of this joke, and it was removed from later versions of the game.

Early in development, Elaine was simply known as The Governor. While writing the wedding scene, Dave Grossman wanted to insert a joke where Guybrush shouts "Elaine!" as a reference to The Graduate. Ron Gilbert, the game's director, liked the joke, and her name became Elaine.

When the troll lifts up his hood to eat the red herring, it will reveal him to be George Lucas, founder of Lucasfilm and LucasArts.

After Guybrush is fired out of the cannon, one of the dialogue choices is "I'm Bobbin. Are you my mother?"
This is a reference to another LucasArts game, Loom. In that game, the main character is named Bobbin Threadbare and he too is looking for his mother.

It was originally intended for Spiffy the Dog to have a close-up, but it was cut from the game due to space restrictions, however it was shown on the back of the game's box. He would eventually receive a close-up in "The Secret of Monkey Island: Special Edition".

Allegedly, Dave Grossman, one of the game's designers, had suggested the idea that the Giant Monkey Head would be a giant robot but the idea was dismissed. The concept would however later be used in the forth installment, "Escape from Monkey Island".

Orson Scott Card, author of the Ender's game series, came up with the insults for the insult sword fighting segments of the game. He received assistance from his kids in coming up with lame starting insults.

Sam & Max appear as an idol to the Giant Monkey Head. Sam & Max were comic strip characters created by Steve Purcell, who was an artist and animator for The Secret of Monkey Island. They also had their own game, developed by LucasArts.

Although the game was made with the intention of the character not being able to die, a gag death exists in the game. If the player stays underwater for ten minutes, Guybrush will drown.

This is a reference to Guybrush's claim that he can hold his breath for ten minutes.

The SCUMM Bar is named after the SCUMM engine used to power the game as well as most of LucasArt's adventure games during the late 1980s and 1990s.