Griffin Keyes (Kevin James) sets up a plan to propose to the love of his life, Stephanie (Leslie Bibb), but she rejects him and claims that his career as a zookeeper is what is keeping her away, therefore breaking Griffin's heart.
Five years later, Griffin is shown to be the lead zookeeper at the Franklin Park Zoo who cares deeply for the zoo animals. That night, Griffin holds a party at the zoo for his brother Dave (Nat Faxon) who is getting married, but freaks out when he discovers that Stephanie was invited. Dave offers Griffin to come and work with him at the car dealership, explaining that it is the best way to win Stephanie. Griffin thinks that he should quit his job at the zoo and join his brother.
Later, the animals hold a meeting saying that they think Griffin is the best zookeeper at the zoo and don't want him to leave, so they decide to find some way to help him win Stephanie's heart. Jerome the bear (Jon Favreau) suggests that they teach Griffin their animal mating techniques, but Joe the lion (Sylvester Stallone) protests, reminding them that it's against the animal code to talk to humans. Donald the monkey (Adam Sandler) says that Stephanie will be at the zoo tomorrow and all the animals have to do is make Griffin look like a hero in front of her.
The next day, Donald unlocks the door to the lion enclosure and lets Joe out, who confronts Stephanie and Dave's fiancee Robin (Steffiana De La Cruz). Kate (Rosario Dawson), the zoo vet manages to get them away from Joe, but Griffin fails to jump into the lion enclosure, ruining the animals' plan. The night afterwards, the animals break their code of silence and tell Griffin that they will teach him what to do to win Stephanie. Griffin learns their different mating rituals, but ends up humiliating himself in front of the other zookeepers and the guests.
Griffin then has a talk with Bernie (Nick Nolte), a forlorn gorilla who was moved into a deep enclosure after allegedly attacking Shane (Donnie Wahlberg), another zookeeper. Bernie explains to Griffin that Shane abuses the animals and he fell when he was abusing Bernie. He lied and said that Bernie attacked him, causing Bernie to lose his trust in anyone.
Griffin discovers that Stephanie is dating her other ex-boyfriend, a bullying alpha-male named Gale (Joe Rogan). Janet (Cher), Joe's wife, tells Griffin that the best way to attract a female is to be seen with another female, so Griffin asks Kate to go on a date with him at Dave and Robin's wedding. Griffin then takes Bernie to T.G.I. Fridays and the two form a friendly bond.
Griffin and Kate go on their date and have a great time together. Griffin becomes brave enough to stand up to Gale and this grabs Stephanie's attention. After Kate tells Griffin she had a great time with him, Stephanie asks Griffin out to dinner. Griffin accepts and they both go to dinner and then go to a fashion show. Stephanie tells Griffin that his job at the zoo is holding him from the outside world, so Griffin decides to quit his job and accepts Dave's offer, which makes Kate upset. Bernie also becomes upset and tells Griffin that he thought he could trust somebody again, but was proved wrong when Griffin quits his job. Kate decides to leave the zoo and go work at a zoo in Africa.
Griffin becomes the best employee at the car dealership, but misses working at the zoo. Stephanie proposes to Griffin, but Griffin refuses and dumps her. He then goes back to the zoo and apologizes to Bernie, who accepts Griffin's friendship. The animals then tell Griffin that Kate is heading to the airport. With the help of Bernie, Griffin manages to catch up with Kate and confesses his love for her. Six months later, Griffin and Kate are back working at the zoo and Bernie is back living in his old enclosure where he gets a great view of the city.