After 26-year-old Kentarou Momose develops health problems due to his boss' abuse, he quits his job and joins a different company. Now, he hopes to start anew under the care of his mentor and direct supervisor, 34-year-old Yuusei Shirosaki. Shirosaki is a capable boss admired by his coworkers, which makes Momose fear letting him down and reliving the past traumas. However, Momose can rest easy, as Shirosaki is always delighted to help—even if he looks absolutely ridiculous doing it. Although it may take some adjusting, Momose realizes that there is no need for caution around his new, endearingly eccentric boss after all.

Subaru Mikazuki is a 23-year-old mystery novel author, major introvert, and an awkwardly shy person. He would much rather stay home to read a book than go outside and interact with others. Further exacerbating this life of solitude, his parents tragically died in an accident many years ago, leaving him alone in the world. One day, while giving offerings at his parents' grave, Subaru runs into a small grey and white cat named Haru, which he ends up taking home with him. Subaru, however, has never taken care of anyone else in his life—can he even take care of a cat? Haru is grateful toward Subaru, as he gives her all the food she wants—a luxury for a cat who is used to a rough life on the streets. But she notices that Subaru can't even seem to take care of himself! Will she be okay with this dunce? Doukyonin wa Hiza, Tokidoki, Atama no Ue. tells the story of an unlikely friendship between a human and a cat who try to foster an understanding with each other.

As Kobayashi sets off for another day at work, she opens her apartment door only to be met by an unusually frightening sight—the head of a dragon, staring at her from across the balcony. The dragon immediately transforms into a cute, busty, and energetic young girl dressed in a maid outfit, introducing herself as Tooru. It turns out that the stoic programmer had come across the dragon the previous night on a drunken excursion to the mountains, and since the mythical beast had nowhere else to go, she had offered the creature a place to stay in her home. Thus, Tooru had arrived to cash in on the offer, ready to repay her savior's kindness by working as her personal maidservant. Though deeply regretful of her words and hesitant to follow through on her promise, a mix of guilt and Tooru's incredible dragon abilities convinces Kobayashi to take the girl in. Despite being extremely efficient at her job, the maid's unorthodox methods of housekeeping often end up horrifying Kobayashi and at times bring more trouble than help. Furthermore, the circumstances behind the dragon's arrival on Earth seem to be much more complicated than at first glance, as Tooru bears some heavy emotions and painful memories. To top it all off, Tooru's presence ends up attracting several other mythical beings to her new home, bringing in a host of eccentric personalities. Although Kobayashi makes her best effort to handle the crazy situation that she has found herself in, nothing has prepared her for this new life with a dragon maid.

As Tooru continues on her quest to become the greatest maid and Kanna Kamui fully immerses in her life as an elementary school student, there is not a dull day in the Kobayashi household with mischief being a daily staple. On one such day, however, a massive landslide is spotted on the hill where Kobayashi and Tooru first met—a clear display of a dragon's might. When none of the dragons they know claim responsibility, the perpetrator herself descends from the skies: Ilulu, the radical Chaos Dragon with monstrous power rivaling that of Tooru. Sickened by Tooru's involvement with humans, Ilulu resorts to the typical dragon method of resolving conflict—a battle to the death. Despite such behavior, she becomes intrigued by Kobayashi's ability to befriend dragons and decides instead to observe just what makes Kobayashi so special. With a new troublesome dragon in town, Kobayashi's eccentric life with a dragon maid is only getting merrier.