In a two player game, at the final boss, Spoiler:if one player answers yes and the other answers no when Mr. X says "Well, you found your way here. Would you consider becoming my right-hand man?", the two players will fight against each other. This is the only way to access the "bad" ending, in which the player takes over the syndicate.

During early stages of the game's development, Axel Stone and Adam Hunter had different names. Axel's name being Hawk and Adam's name being Wolf.

In a 1991 interview with BEEP Mega Drive Magazine, the game's composer Yuzo Koshiro stated that he started writing the music for the game at the end of 1990. He often went dancing at clubs, and at the time, the scene was moving on from Eurobeat to a new trend: house music. Because Streets of Rage was a beat 'em up game, he wanted the music to be energetic and exciting, and initially thought about writing a rock soundtrack for the game. However, when he first tried using house music in the game, "it all clicked, and [he] thought it sounded really cool."

On the game's Japanese cover, illustrated by Yoshiaki Yoneshima. Blaze Fielding's pose strongly resembles the same pose made by Hitomi Kisugi in an illustration by mangaka Tsukasa Hojo for a 1994 10 aizōban re-release of Shonen Jump's Cat's Eye.