God is, according to many monotheistic religions, the Almighty Ruler and creator of the Universe. He resides in Heaven. His face is never shown on screen, except for a couple of occasions. See below for details.
God makes his first appearance in "Homer the Heretic", when Homer falls asleep suddenly and has a dream in which he personally appears to him. God is very angry at Homer for "forsaking his church." Homer points out that he's not a bad guy, as he works hard and loves his children, and questions why he should spend half his Sunday hearing about how he's going to hell. After a brief chat about football, Homer explains that what bugs him most about church is the sermons, where God couldn't agree more. He mentions that Reverend Lovejoy really displeases him and that He'll give him a canker sore. In the end, God agrees with Homer's point and agrees to let Homer worship in his own way.
In "Mr. Plow", after Homer reconciles with Barney and decide to join forces with him as partners in their respective plowing businesses, Homer mentions, "When two best friends work together, not even God Himself can stop them." God then replies, "Oh, no?" He causes the sun to suddenly appear, which melts away all the snow, and puts the both of them out of business.
In "A Star is Burns", Ned Flanders calls on God's aid to help him save Todd from being swept away by a deadly river. Surprisingly, he is quick to help the Flanders family and even gives Ned an "OK" gesture from Heaven which Ned responds with a friendly gesture of his own.
In "Pray Anything", after Homer sues the church, he receives the deed to it as part of his award, and turns it into a sleazy hangout place, where all Ten Commandments are broken; the town begins to flood. As the flood starts to rise, Reverend Lovejoy returns in a helicopter and leads everyone in prayer, asking God to forgive them for letting themselves be led by a "demon in blue pants." 
In "Thank God It's Doomsday", after Homer arrives in Heaven, and sees Marge and his children being tormented by the Devil, he has a talk with God about saving his family. When God refuses to help, due to Jesus' suffering on Earth, Homer becomes angry and runs around vandalizing Heaven in an attempt to change God's mind. God finally agrees to undo the Rapture by turning back time, and restores Moe's Tavern.
God serves as the final boss to The Simpsons. He uses previous enemies encountered as icons in a "Guitar Hero"/"Dance Dance Revolution" match, while the chosen song ("Rock you Like a Hurricane", by the Scorpions) plays. As the whole family, you have to make them hit the notes in a correct time to break the game stations and defeat the minions he sends. They will change when the station is broken. Each station is a parody of a popular videogame console (i.e.: Praystation is a parody of PlayStation and the Hii is a parody of the Wii).
God is also portrayed by Ned Flanders' hand.
- In most of God's appearances in the various Simpsons media, his face is covered up (presumably deliberately). There were, however, two instances where his face was fully seen; in the opening of "Treehouse of Horror XVI" (when he hangs on to the edge of the universe after Kang and Kodos decide to destroy everything), and in the frame Ned Flanders turns around in "Alone Again, Natura-Diddily".
- In the Simpsons universe, God exists, meaning that in the Simpsons universe, the universe was created by God, implying that "The Big Bang Theory" or any other possibilities of how the universe began, is false.
- Unlike everyone else in the Simpson universe, God has five fingers on each hand and five toes on each feet. This is confirmed to be intentional on the DVD commentary for "Homer the Heretic".
- His son, Jesus Christ, is sometimes shown to share this trait, but not consistently.
- In the final scene of "Homer the Heretic" he is shown with only four fingers like the other characters, but this is an error.
- Some fans believe that the highly mathematical cast of writers on the Simpsons (as described by Simon Singh's book "The Simpsons and their Mathematical Secrets") put this Easter Egg into the show for the reason that Homer and co. lives in a based 10 world despite having 4 fingers on each hand. In the real world, many believe that based 10 came about in math due to us humans having 10 fingers. In the Simpsons world, when God or Jesus has 10 fingers, 5 on each hand, it makes them unique (as they should be as divine beings).