When starting a new game, a short movie detailing the creation of the Earth and the rise of humankind is played while the map is generated. This movie is a remake of the opening to the original Sid Meier's Civilization, with updated visuals and music, as well as narration by the late Leonard Nimoy.

In the Chinese version of Civilization IV, Mao Zedong was replaced by Emperor Taizong of the Tang, presumably because the government of the People's Republic of China did not want players to declare war on the founder of their nation.

Series creator Sid Meier appears as the instructor in the gameplay tutorial, providing both his likeness and his voice.

In 2011, Civilization IV became the first video game to win a Grammy Award. The main theme, "Baba Yetu", was originally composed by Christopher Tin for an album named "Calling All Dawns", but it was used in Civilization IV before the album's release. The song won Best Instrumental Arrangement with Accompanying Vocalists.

The opening theme to the games is called "Baba Yetu" and is actually the Lord's Prayer sung in Swahili.