Frankenstein begins with the messages of Captain Robert Walton to his sister. These letters form the framework for the story in which Walton tells his sister the story of Victor Frankenstein and his monster as Frankenstein tells it to him. Walton sets out to explore the North Pole. The ship becomes trapped in frozen water and the crew, watching around them, observes a giant man in the distance on a dogsled. Hours later they find Frankenstein and his own dogsled near the ship, so they bring the sick man aboard. As he recovers, Frankenstein tells Walton his story.

Frankenstein grew up with close ties to his adopted cousin, Elizabeth, and his friend Henry Clerval. As a young boy, Frankenstein becomes obsessed with studying outdated theories about what gives humans life. In college at Ingolstadt, he creates what he considers a paragon of humanity from scavenged body parts, but upon bringing it to life, realizes the creature is hideous. Disgusted by and fearful of the monster's appearance, Frankenstein flees.

Henry Clerval comes to Ingolstadt to study with Frankenstein, but ends up nursing him after his exhausting and secretive efforts to create a human life. While Frankenstein recovers from his illness over many months and then studies languages with Clerval at the college, the monster wanders around looking for friendship. After several harsh encounters with humans, the monster becomes afraid of them and spends a year living near a cottage and observing the family who lived there. Through these observations he becomes educated and self-aware and realizes that he is very different in physical appearance from the humans he watches. In loneliness, the monster seeks the friendship of this family, but they are afraid of him, and this rejection makes him seek vengeance against his creator. He travels to Rome and meets a little boy in the woods. In the vain hope that because the boy is still young and potentially unaffected by older humans' perception of his hideousness, the monster hopes to kidnap him and keep him as a companion, but the boy reveals himself as Frankenstein's younger brother, so the monster kills him in his first act of vengeance against his creator. The monster plants a necklace he removes from the child's body on a girl, who is later executed for the crime.

When Frankenstein learns of his brother's death, he returns to Geneva to be with his family. In the woods where his young brother is murdered, Frankenstein sees the monster and becomes sure that he is William's murderer. Frankenstein, ravaged by his grief and guilt for creating the monster who wreaked so much destruction, retreats into the mountains alone to find peace. After a time in solitude, Frankenstein is approached by the monster. Initially furious and intending to kill it, Frankenstein composes himself upon the monster's pleading. The monster delves into an exhaustive narrative of his short life, beginning with his creation, which fashions an impression of him as an initially harmless innocent whom humans abused into wretchedness. He concludes his story with a demand that Frankenstein create for him a female counterpart, reasoning that no human will accept his existence and character due to his hideous outer appearance. He argues that as a living thing, he has a right to happiness and that Frankenstein, as his creator, has the duty to facilitate it. Frankenstein, fearing for his family, reluctantly agrees and travels to England to do his work. Clerval accompanies Frankenstein, but they separate in Scotland. In the process of creating a second being, Frankenstein becomes plagued by the notion of the carnage another monster could wreak and destroys the unfinished project. The monster vows revenge on Frankenstein's upcoming wedding night. Before Frankenstein returns home, the monster murders Clerval.

Once home, Frankenstein marries his cousin Elizabeth and, in full knowledge of and belief in the monster's threat, prepares for his death. Instead, the monster kills Elizabeth; the grief of her death killed Frankenstein's father. After that, Frankenstein vowed to pursue the monster until one destroyed the other. Over months of pursuit, the two end up in the Arctic Circle near the North Pole. Here, Frankenstein's narrative ends and Captain Walton assumes the telling of the story again. A few days after Frankenstein finishes his story, Walton and his crew decides to turn back and go home. Before they leave, Frankenstein dies and the monster appears in his room. Walton hears the monster's sorrowful justification for his vengeance as well as expressions of remorse before he leaves the ship and travels toward the Pole to destroy himself so that none would ever know of his existence.

    《弗兰肯斯坦》梗概
　　
　　作品以四封信为开篇。
　　
　　这些信件叙述了作者在北极探险时所遇到的一个怪人讲述的故事。
　　
　　原来，这个人是瑞士贵族弗兰肯斯坦，他曾留学德国，研究电化学和生命，发现了死亡的秘密，于是决定着手制造生命。他先从尸体中寻找材料，然后进行组装，最后借助电化学方法予以激活。但是，本来全都是由好材料制造的、高达8英尺的怪物在被赋予了生命之后，却变得奇丑无比，弗兰肯斯坦被吓得昏了过去，醒来之后发现怪物已经失踪。
　　
　　其实怪物刚刚诞生时还是十分热爱这个世界的，他躲藏在山里并学会了使用火，并遇到隐居在山中的一位盲爷爷和一对青年男女，由此受到感动，开始热爱人类社会。怪物白天趁青年男女外出时偷偷帮助盲爷爷打柴，并偷出书来自学了阿拉伯语和法语等各种语言，阅读了《少年维特之烦恼》等大量文学和哲学名著，于是开始渴望艺术和爱情。但他同时又十分感慨自己现在的情况，认为“撒旦才代表我目前的处境”，强烈地希望能够改变现状。于是怪物潜入这一家中，发现只有盲爷爷在家，便与之海阔天空地聊了起来；这时青年男女突然归来，小伙子气愤地把它打出门去。这严重地伤害了怪物的自尊心，他冷静后想到，自己与其向别人求情，还不如去找缔造者。但它刚一出现在大街上，就受到了很多人的打骂，屡屡遭到大家的厌恶和恐惧，甚至有人朝它开枪。怪物终于丧失了最后一丝善良，认为这一切都来源于它的制造者。
　　
　　从此阴影便开始笼罩在了弗兰肯斯坦身上。怪物杀死了他的弟弟，又嫁祸于女仆。弗兰肯斯坦赶到现场后，终于发现这些都系怪物所为，于是开始了对怪物的追逐，一直追到阿尔卑斯山上。怪物认为自己没有受到公平的待遇，得不到异性的爱。“我要获得一切”。因此它要求弗兰肯斯坦再为它造一个女人，然后两人一同远离人世。
　　
　　弗兰肯斯坦开始同意了，但在造好通电的那一刹那，他突然产生了犹豫：如果它们真的恋爱繁衍，又会给人类带来多么大的麻烦？于是他马上毁掉了女怪物。怪物看到这一切后暴跳如雷，对人类社会和自己的前途彻底绝望，杀死了弗兰肯斯坦的好友，又在婚礼上杀死了弗兰肯斯坦的新娘。而这时弗兰肯斯坦也愤怒了，两人开始了互相追杀，一直追逐到北极……
　　
　　最后的结局是，造物主弗兰肯斯坦在对作者讲述完这一切后终于死去，而这时从远方走来一个大个子，爬在放弗兰肯斯坦尸体的雪橇上忏悔，然后声称报仇结束，义无反顾地走向冰原……