Tomoya Okazaki is a delinquent who finds life dull and believes he'll never amount to anything. Along with his friend Youhei Sunohara, he skips school and plans to waste his high school days away. One day while walking to school, Tomoya passes a young girl muttering quietly to herself. Without warning she exclaims Anpan! (a popular Japanese food) which catches Tomoya's attention. He soon discovers the girl's name is Nagisa Furukawa and that she exclaims things she likes in order to motivate herself. Nagisa claims they are now friends, but Tomoya walks away passing the encounter off as nothing. However, Tomoya finds he is noticing Nagisa more and more around school. Eventually he concedes and befriends her. Tomoya learns Nagisa has been held back a year due to a severe illness and that her dream is to revive the school's drama club. Claiming he has nothing better to do, he decides to help her achieve this goal along with the help of four other girls. As Tomoya spends more time with the girls, he learns more about them and their problems. As he attempts to help each girl overcome her respective obstacle, he begins to realize life isn't as dull as he once thought.

For the last three years, Teikou Middle School has dominated the national basketball scene with its legendary lineup: the Generation of Miracles. It consisted of five prodigies who excelled at the sport, but a Phantom Sixth Man lurked in the shadows and helped earn the team their revered status. Eventually, their monstrous growth jaded them from the sport they loved and made them go their separate ways in high school. In search of new members, the Seirin High School basketball team recruits Taiga Kagami and Tetsuya Kuroko, two freshmen who seem to have significant differences in abilities. Having returned recently from America, Kagami has both a natural aptitude and relentless love for the sport. Meanwhile, Kuroko lacks presence and exhibits no outstanding athletic talent. However, it is later revealed that he is Teikou's Phantom Sixth Man—the player once part of the Generation of Miracles. Kuroko wants to prove to the Seirin team that he is strong in his own way. Seeing his conviction, Kagami forms a dynamic partnership with Kuroko, the latter promising to support Kagami's light as his shadow. Alongside their new Seirin teammates, they aim to conquer the upcoming Interhigh championship, but the reappearance of Kuroko's former teammates complicates their plan.

With the Interhigh Championship finally over, Seirin's basketball team refocuses their efforts, training harder than ever to get the chance to participate in the Winter Cup. Both Tetsuya Kuroko and Taiga Kagami see old friends walk back into their lives, providing a challenge both on and off the court. As new skills are developed and new alliances created, enemies from various teams—giants of high school basketball such as Yousen, Shuutoku, and Touou—stand in the way of Seirin's steadfast attempts to get to the top. All of these schools prove to be formidable foes whose abilities progress exponentially, while Kuroko struggles to find a balance between his resolve to play as part of a team and his desire to win. With old wounds reopening, new challenges to face on the court, and a new set of foes—the Uncrowned Kings—vowing to defeat the new hopefuls, will Seirin ever be able to achieve their dream of beating the Generation of Miracles?

Seirin prepares to face major obstacles on their path to winning the Winter Cup, including the teams each possessing a member of the Generation of Miracles. Kuroko goes head-to-head with his old teammates once more as he attempts to show them that individual skill is not the only way to play basketball. His firm belief that his form of basketball, team play, is the right way to play the sport will clash with the talents of a perfect copy and an absolute authority. While Kuroko tries to prove that his basketball is right, he and the rest of Seirin High ultimately have one goal: to win the Winter Cup and overcome the strength of the Generation of Miracles, who have long dominated the scene of middle and high school basketball.