Spurred by handbills which stated that agricultural workers were badly needed in California, the Joads, along with thousands of others, made their tortuous way, in a worn out vehicle across the plains toward the mountains. Grampa died of a stroke during their first overnight stop. And, to add to the general misery, returning migrants told the Joads that there was no work to be had in California, that conditions were even worse than they were in Oklahoma. But the dream of a bountiful West Coast urged the Joads onward.
Close to the California line, where the group stopped to bathe in a river, Noah, feeling he was a hindrance to the others, wandered away. It was there that the Joads first heard themselves addressed as Okies, another word for tramps.
Granma died during the night trip across the desert. After burying her, the group went into a Hooverville, as the migrants’ camps were called. There they learned that work was all but impossible to find. A contractor came to the camp to sign up men to pick fruit in another county. When the Okies asked to see his license, the contractor turned the leaders over to a police deputy who had accompanied him to camp. Tom was involved in the fight which followed. He escaped, and Casy gave himself up in Tom’s place. Connie, husband of the pregnant Rose of Sharon, suddenly disappeared from the group. The family was breaking up in the face of its hardships. Ma Joad did everything in her power to keep the group together.
The Joads left Hooverville and went to a government camp maintained for transient agricultural workers. For the first time since they had arrived in California, the Joads found themselves treated as human beings.
Circumstances eventually forced them to leave the camp, however, for there was no work in the district. They drove to a large farm where work was being offered. There they found agitators attempting to keep the migrants from taking the work because of unfair wages offered. But the Joads, thinking only of food, were escorted by motorcycle police into the farm. The entire family picked peaches for five cents a box and earned in a day just enough money to buy food for one meal. Tom, remembering the pickets outside the camp, went out at night to investigate. He found Casy, who was the leader of the agitators. While Tom and Casy were talking, deputies, who had been searching for Casy, closed in on them. The pair fled, but were caught. Casy was killed. Tom received a cut on his head, but not before he had felled a deputy with an ax handle. The family concealed Tom in their shack. The rate for a box of peaches dropped, meanwhile, to two-and-a-half cents. Tom’s danger and the futility of picking peaches drove the Joads on their way. They hid the injured Tom under the mattresses in the back of the truck.
The family found at last a migrant crowd encamped in abandoned boxcars along a stream. They joined the camp and soon found temporary jobs picking cotton. Ma, realizing that Tom was not safe, sent him away.
The Autumn rains began. Soon the stream which ran beside the camp overflowed and water entered the boxcars. Under these all but impossible conditions, Rose of Sharon gave birth to a dead baby. When the rising water made their position no longer bearable, the family moved from the camp on foot. The rains had made their old car useless. They came to a barn, which they shared with a boy and his starving father. Rose of Sharon, bereft of her baby, nourished the famished man with the milk from her breasts. So the poor kept each other alive in the depression years.
在《愤怒的葡萄》一书中，斯坦贝克不时打断故事的叙述，插进一些简练的、印象式的段落，取得有趣的对位衬托效果，仿佛是在用一架电影照相机作纪录似的，很快从一幕场景换为另一幕场景，从一个焦点转到另一个焦点。这本小说是对我们的资本主义经济的强烈控诉、也是对西南部农民糟蹋土地的尖锐批评。《愤怒的葡萄》的特色在于它逼真地，详细地，虽然有时是自作多情地，描绘了二十世纪三十年代中期大沙窝地区美国农民的情况。
汤姆·乔德从俄克拉何马州立监狱中释放出来，他是由于自卫杀人在那座监狱里服刑的。他穿过一片由干旱和沙暴造成的荒凉不毛的地区。在旅途中，他遇到了吉姆·凯西，一名前传教士。他们两人结伴来到汤姆家人的住处时，发现乔德老家已经无人居住。正当他们对情况捉摸不透时，一个顽固的名叫莫利·格雷夫斯的佃农走来，从他口中得知，这一带所有的人家都已经或正打算去加利福尼亚。莫利还告诉他们说汤姆的亲属也已经搬到一个亲戚那里准备到西部去。莫利是唯一留下不走的佃农。
由于土地银行、天气和机器耕作等种种原因，南方所有中西部各州无法谋生的农民不是卖掉了土地，便是被迫退出他们租佃的土地。经营废旧品和推销旧汽车的商人在他们这些人身上发了横财。成千上万的家庭踏上了通向希望之乡——加利福尼亚的大路。
汤姆和凯西在约翰叔叔家里找到乔德一家人，看到他们也正忙于打点动身去加利福尼亚。约好一起动身的人当中有乔德爸和乔德妈、他们那个脑筋迟钝的儿子诺亚，有汤姆和诺亚还未成年的小弟弟艾尔，有汤姆的妹妹沙伦玫瑰和妹夫康尼；还有乔德家的孩子们罗瑟和温菲尔德、乔德奶奶和乔德爷爷。艾尔买了一辆古老的卡车好载着他们一路到西部去。这家人请吉姆·凯西和他们一道走。
一路上看到许多传单说加利福尼亚迫切需要农业工人。受到这个消息的鼓舞，乔德一家乘着一辆老掉牙的车子与成千上万的人家一起沿着曲折的道路，超过平原走向山区。他们第一天停下来过夜的时候，爷爷突然中风死了。苦难的事还不止这些，折回来的流民告诉乔德一家说在加利福尼亚根本找不到什么活干，那儿的情况甚至比俄克拉何马州还要糟。然而，对富饶的西海岸的梦想激励着乔德一家继续前进。
当他们接近加利福尼亚州的州界时，停下来在一条河里洗澡。诺亚觉得自己成了别人的一个累赘，就悄悄地溜走了。就是在这个地方，乔德这家人第一次听到人家管他们叫做欧开伊，这是对流浪农业工人的另一种称呼。
在穿过沙漠的当天晚上，奶奶死了。他们埋葬好了奶奶之后，走进了一个胡佛村，这是流民宿营地的一个别名。在那儿，他们听说找工作几乎是一件办不到的事。一个包工头来到营地要招工到另一个县里去摘水果，当这些欧开伊们要他拿出执照来看时，这个包工头把几个欧开伊头头交给陪他同来营地的治安队员。汤姆被卷进随后发生的冲突中，他逃脱了。凯西代替汤姆投案自首。这时候，怀着身孕的沙伦玫瑰的丈夫康尼突然离开大家走了。这家人在艰难困苦面前眼看就要四分五裂了。乔德妈尽她所能把全家团结在一起。
乔德一家人离开了胡佛村去到一所政府为过路的流动农业工人设立的营地。自从他们来到加利福尼亚以后，这是乔德一家子第一次觉得他们被当作人对待。
然而，环境终于迫使这家人离开营地，因为这个地区实在找不到工作。他们驱车来到一处正需要劳工的大农场。在那里他们发现有人在进行宣传鼓动，想要劝阻流民不去上工，因为农场所给的工资不公道。但是，一心只考虑填饱肚子的乔德一家人，却由骑着摩托车的警察护送进入农场。全家人摘桃子，五分钱一箱，可是干一整天赚的钱只能买一顿饭。汤姆想起在营地外面的罢工纠察队员，趁夜晚溜出去打听情况。他碰到凯西，凯西这时已经是那些鼓动家的头头了。他们俩正在说话的时候，被一直在搜寻凯西的治安队员所包围。两人夺路逃跑，可是不幸身陷重围。凯西被杀身亡，汤姆头上挨了一刀，不过他总算先用斧柄打倒了一名治安队员。家里人把汤姆藏在窝棚里。在这段时间里，摘桃子的工钱跌到了两分半一箱。汤姆的危险处境，同时摘桃子又实在无法维持生活，于是乔德这一家人只好重新上路，将受伤的汤姆藏在卡车后面的垫子底下。
最后，这家人看到有一群流民在一条小河边几辆被遗弃的棚车里安营扎寨。他们加入了这一伙，不久就找到摘棉花的临时工作。乔德妈意识到汤姆处境不安全，就打发他走了。
秋雨开始了。不久，流经营地旁边的河水四处泛滥，漫进了棚车。在这种简直活不下去的情况下，沙伦玫瑰生下了一个死婴。涨上来的水使这家人再也无法忍受。连日大雨使他们那辆老汽车全无用处，一家人只好徒步离开那个营地。他们路过一处谷仓，便在那里同一个男孩和他正在挨饿的父亲挤在一起。失掉自己婴儿的沙伦玫瑰用她的乳汁喂养那个快要饿死的男子。穷人们就是这样在大萧条的岁月里相依为命的。