The Irish-American, Catholic Sullivan brothers are introduced through a progression of baptisms: George Thomas in 1914, Francis "Frank" Henry in 1916, Joseph Eugene in 1918, Madison "Matt" Abel in 1919, and Albert Leo in 1922 in their hometown of Waterloo, Iowa. There is also sister Genevieve, nicknamed "Gen", making the Sullivans a happy family of eight. As the boys grow, they are doted upon by their mother and sister Genevieve and given stern but loving guidance by their father, who is a railroad freight conductor. Each day, the boys climb the water tower by the tracks and wave to their father as he passes by on the train. The brothers are shown getting into their fair share of trouble growing up: a fight, a near drowning (after which their mother makes them promise not to set foot on a boat again until they are adults), and accidentally flooding the kitchen.
Skipping forward to 1939, only Al is still in high school. On the day that George wins a motorcycle race for the local motorcycle club The Black Hawks, Al meets Katherine Mary, (Anne Baxter) an only child who lives with her father. Despite their youth, Al and Katherine Mary fall in love. Believing that Al is too young, his brothers nearly break the couple up, but realize what they have done and apologize. Soon after, Katherine Mary and Al are married, and ten months later, are expecting a baby. Al is fired for taking the afternoon off to escort his wife to the doctor, but his brothers vow to help them out.
Later, months after little Jimmy has been welcomed into the family, the Sullivans are relaxing on a Sunday December 7, 1941. They hear about the attack on Pearl Harbor on the radio. The boys realize that one of their friends, Bill Bascom (Bill Ball in real life), was on the USS Arizona and resolve to join the Navy to avenge him. Al decides that he cannot go with his brothers, due to his family responsibilities, but when Katherine Mary sees his despondent face, she tells him to go with the others to the recruiting station. The brothers insist that they serve on the same ship, but the recruiter states that the Navy can make no such guarantees. The brothers leave, but later, George receives his draft notice to report for military service to the U.S. Army. George writes to the Navy Department, obtaining official permission for the boys to serve together.
Later, Tom, Alleta, and Katherine Mary eagerly await letters from their loved ones, who are serving aboard the USS Juneau in the Pacific. On November 13, 1942, a battle rages off the Solomon Islands, and the Juneau is hit with a torpedo. Four of the brothers find each other, then realize that the wounded George is below in sick bay. They rush down to get him when the call to abandon ship is ordered. When George insists they leave him behind, Al replies, "We can't go swimming without you." Just then, another enemy torpedo hits the ship as it is being evacuated and the ship explodes in a massive fireball, killing all of the crewmen left on board.... including all five of the Sullivan brothers.
A few days alter, the same recruiter from before visits the Sullivan home and tells Katherine Mary, Tom, Alleta, and Gen that all five of the brothers were killed in action. Stunned, Tom goes to work and salutes the water tower on which his sons used to stand and wave to him. Sometime later, Tom, Katherine Mary, and Gen, who has joined the WAVES, watch with pride while Alleta christens a new destroyer, the USS The Sullivans. As Tom and Alleta watch the ship sail away, Alleta declares, "Tom, our boys are afloat again."