Ramy is a young Muslim American who is trying to go on a date. His exploration of the world of relationships leads to a date with a fellow Muslim American who turns out to be sexually aggressive and kinky, much to Ramy's shock.
When Ramy loses his job at a tech startup, his parents convince him to take a job with his uncle Naseem. The only problem is that his uncle is a sexist conspiracy theorist who can not stop hypothesizing about 9/11.
Despite his friends' objections, Ramy becomes involved with a Jewish American who eventually leaves him for another when he refuses to do drugs with her.
Ramy reflects on how the 9/11 attacks changed his life and affected his relationships. Due to his Muslim faith, he is shunned by his friends and has to take another route to school, where he ends up meeting his best friend.
As the holy month of Ramadan approaches, Ramy has every intention to abide by its religious rules, including fasting and abstaining from vices. His plans are shot to hell when he meets a lonely Muslim woman at the mosque and ends up sleeping with her at her house.
As Dena agonizes over still being a virgin, she decides to follow her friends' advice and meet up with the flirty local barista. But things do not go well when they end up at his apartment.
The lonely Maysa takes a risk and becomes a Lyft driver. Her hopes of meeting new people are jeopardized when she has trouble getting her fellow drivers to accept her. This only changes when one of her passengers takes a liking to her because she speaks his language.
Stevie persuades Ramy to accompany him when he goes to meet Mikaela whom Stevie met online. They are shocked to discover that Mikaela is a high school student. The day takes a turn for the worse when Mikaela passes out after consuming alcohol, leaving Ramy and Stevie scrambling to save her.
Searching for his identity and the origins of his faith, Ramy goes to visit relatives in Egypt. His plans to sightsee and pray in the local mosques are derailed by his Americanized cousin Shadi, who just wants Ramy to come to parties and do drugs with him.
Ramy's trip to see his grandfather in the countryside keeps getting disrupted, first by a broken car and then by his grandfather's death soon thereafter. At the funeral, Ramy meets his cousin Amani and they start falling for each other.