In the 1950s, a feral puppy wonders about life's true purpose. Weeks later, he is caught by dogcatchers, whisked away to the pound, and euthanized.
The dog is reborn as a Red Retriever in 1961. Leaving his cage at a puppy mill, he is taken by two garbage men, who plan to sell him. Left locked inside their pick-up truck, he begins to die of heatstroke, but is rescued by a kindhearted mother and her eight-year-old son, Ethan Montgomery. They break the truck's window and bring him home, naming him Bailey. Bailey and Ethan bond quickly, especially over the summer at Ethan's grandparents' farm, and Bailey decides Ethan alone is his purpose. Ethan gives him the nickname “Boss Dog”. Years pass, and after several attempts at advancing in his job fail, Ethan's father has become an alcoholic. In 1969, Ethan meets a girl named Hannah at a fair with Bailey, and they soon begin dating. They spend their summer together, happily, through senior year. They plan to go to the same college, Ethan getting a football scholarship and Hannah with an academic one. At home one night, Ethan's drunken father becomes abusive towards his mother and him. Ethan kicks him out. Later in 1971 at a football game watched by scouts, Ethan is offered a full scholarship to Michigan State University. That night, his vindictive classmate Todd throws a lit firecracker into Ethan's house, causing a house fire. Bailey alerts Ethan, who saves his mother out through an upstairs window. Ethan lowers her, then Bailey. However, he loses his rope and must jump, fracturing his leg and ending his athletic scholarship. Bailey attacks Todd, who is arrested by the police when firecrackers fall out of his pocket. Now, Ethan must go to an agricultural school, where he will learn to take over the farm. Depressed, Ethan breaks up with Hannah before leaving for college, while Bailey stays with Ethan's grandparents. Bailey ages and Ethan comes to say goodbye.
Bailey is reborn as a female German Shepherd puppy, growing into a police dog named Ellie, in the late 1970s/early 1980s, while fully retaining memories of her past lives. Ellie is partnered with lonely officer Carlos Ruiz who has recently split up with his partner, of the Chicago Police Department, and works hard at "seeking" and "finding", now seeing the job as life's purpose. They form a close bond, ending after Ellie saves a girl, kidnapped by her mother's ex-boyfriend, from drowning and is then fatally shot by the kidnapper while protecting Carlos.
Reborn in the mid-1980s as a male Corgi, Bailey is adopted by Atlanta college student Maya, who names him Tino. Lonely, he tries to find her happiness. She meets Al, a classmate, after Tino falls for Al's dog, a female Landseer named Roxy. They marry, having three children. Tino is heartbroken when one day Roxy does not return from the vet. As Tino ages and dies, he thanks Maya for giving him one of his best lives.
Bailey reincarnates again, this time as a St. Bernard/Australian Shepherd mix puppy in 2014. At first adopted by a woman named Wendi, he is named Waffles. Unfortunately, Wendi's husband neglects him, refuses to let her keep him inside, and after several years, abandons him. Waffles searches for a new life, gradually making his way back to where he spent summers as Bailey. He joyfully reunites with his old master Ethan, now in his 60s, lonely on his grandparents' old farm, now his. Not recognizing him, Ethan takes him to the local animal shelter, but later reclaims him, naming him Buddy. Sensing that he has finally found his true purpose, he reunites Ethan with a widowed Hannah, and they get married. Buddy shows Ethan that he is his “Boss Dog”, by performing tricks and responding to phrases that were known only to the two of them many years back. Ethan finds Bailey's collar, now old and rusty, and places it back on Bailey's neck, and they resume playing exactly the way they did so long ago. Bailey narrates that life is about having fun, saving others, finding someone to be with, not getting upset over the past or the future, and living for today.