深夜的穆赫兰道发生一桩车祸，女子丽塔（劳拉·哈灵 饰）在车祸中失了忆。她跌跌撞撞来到一个公寓里藏身。
一名男子说他长常常梦见一个叫云奇的地方，那里有个恶魔盯着他。于是就来到云奇，果真见到墙后有怪物出现，男子当场晕死。
另有一名杀手杀死了他面前的男人，然而蹩脚的他却惹来了不少一连串的麻烦。...
故事回到一个刚到好莱坞“寻梦”的女子贝蒂（娜奥米·沃茨饰），她的姨父姨母在电影圈有广泛人缘，让贝蒂的发展如虎添翼，试镜大受好评。同时，她所住的公寓，正好是丽塔藏身之地。贝蒂收留了丽塔，二人感情融洽。面对记不起自己是谁的丽塔，贝蒂决定帮助她寻找回自己的记忆。
一名导演想自己决定新戏的女主角，却被他人强行安排人选。工作不顺意的他还发现妻子和清洁工睡在一起。 这些看似松散的事件，就像一个迷宫，引向一个让人猜不透的世界……
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