After a meteor falls in Northeast Italy in 2077, creating a major disaster, the government of Earth sets up the Spaceguard system as an early warning of arrivals from deep space.
The "Rama" of the title is an alien starship, initially mistaken for an asteroid categorised as "31/439". It is detected by astronomers in the year 2131 while it is still outside the orbit of Jupiter. Its speed (100,000 km/h) and the angle of its trajectory clearly indicate it is not on a long orbit around the sun, but comes from interstellar space. The astronomers' interest is further piqued when they realise the asteroid has an extremely rapid rotation period of 4 minutes and is exceptionally large. It is named Rama after the Hindu god, and an unmanned space probe dubbed Sita is launched from the Mars moon Phobos to intercept and photograph it. The resulting images reveal that Rama is a perfect cylinder, 20 kilometres (12 mi) in diameter and 54 kilometres (34 mi) long, and completely featureless, making this humankind's first encounter with an alien spacecraft.
The manned solar survey vessel Endeavour is sent to study Rama, as it is the only ship close enough to do so in the brief period Rama will spend in our solar system. Endeavour manages to rendezvous with Rama one month after it first comes to Earth's attention, when the alien ship is already inside Venus' orbit. The 20+ crew, led by Commander Bill Norton, enters Rama through triple airlocks, and explores the vast 16-km wide by 50-km long cylindrical world of its interior, but the nature and purpose of the starship and its creators remain enigmatic throughout the book. The astronauts discover that Rama is hollow, and that its inner surfaces hold vast "cities" of geometric structures that resemble buildings and are separated by streets with shallow trenches. A mammoth band of water, dubbed the Cylindrical Sea, stretches around Rama's central circumference. Massive cones, which the astronauts theorize are part of Rama's propulsion system, stand at its 'southern' end. They also find that Rama's atmosphere is breathable.
One of the crew members, Jimmy Pak, who has experience with low gravity skybikes, volunteers to ride a smuggled skybike along Rama's axis to the far end, otherwise inaccessible due to the cylindrical sea and the 500-m high cliff on the opposite shore. A few hours later, Jimmy reaches the massive metal cones on the southern end of Rama, and detects a strange magnetic field coming from the cones. He takes some photos of the area and the strange plateau on the southern end of Rama's landmass. As he leaves the area, the electrical charge in its atmosphere increases, resulting in lightning. A discharge hits his skybike, causing him to crash on the isolated southern continent.
When Pak wakes up, he sees a crab-like creature picking up his skybike and chopping it into pieces. He cannot decide whether it is a robot or a biological alien, and keeps his distance while radioing for help. As Pak waits, Norton sends a rescue party across the cylindrical sea, using a small, improvised craft, constructed earlier for exploration of the sea's central island. Pak sees the crablike creature dump the skybike's remains into the sea. The creature then walks toward but ultimately ignores him. Pak explores the surrounding fields while waiting for the rescue party to arrive on the southern cliffs of the cylindrical sea. Amongst the strange geometric structures, he sees an alien flower growing through a cracked tile in the otherwise sterile environment, and decides to take it as both a curiosity and for scientific research.
Pak jumps off the 500 m cliff, his descent slowed by the low gravity and using his shirt as a parachute, and is quickly rescued by the waiting boat. As they ride back, tidal waves form in the cylindrical sea, created by the movements of Rama itself as it makes course corrections. When the crew arrives at base, they see a variety of odd creatures inspecting their camp. When one is found damaged and apparently lifeless, the team's doctor/biologist Surgeon-Commander Laura Ernst inspects it, and discovers it to be a hybrid biological entity and robot—eventually termed a "biot". It, and by assumption the others, are powered by natural internal batteries (much like those of terrestrial electric eels) and possess some intelligence. They are believed to be the drones of Rama's still-absent builders.
The members of the Rama Committee and the United Planets, both based on the moon, have been monitoring events inside Rama and giving feedback. The Hermian colonists have concluded that Rama is a potential threat and send a rocket-mounted nuclear bomb to destroy it should it prove to pose a threat, but Lt. Boris Rodrigo uses a pair of wire cutters to defuse the bomb and its control.
As Rama approaches perihelion, the biots jump into the cylindrical sea, where they are destroyed (or recycled) by aquatic biots ('sharks') and reabsorbed into the mineral-laden water. On their final expedition, some crew members decide to visit the city christened "London" (as it is closest to Rama's "northern" end, the point of their entry), where they use a laser to cut open one of the "buildings" to see what it houses. They discover transparent pedestals containing holograms of various artefacts, which they theorize are used by the Ramans as templates for creating tools and other objects. The most amazing of these appears to be a uniform with bandoliers, straps and pockets that suggests the size and shape of the Ramans. As the crew photographs some of the holograms, the six gigantic striplights that illuminate Rama's interior start to dim, prompting the explorers to leave and re-board Endeavour.
With Endeavour a safe distance away, Rama reaches perihelion and utilizes the Sun's gravitational field, and its mysterious "space drive", to perform a slingshot manoeuvre which flings it out of the solar system and toward an unknown destination in the direction of the Large Magellanic Cloud.
The book was meant to stand alone, although its final sentence suggests otherwise:
And on far-off Earth, Dr. Carlisle Perera had as yet told no one how he had wakened from a restless sleep with the message from his subconscious still echoing in his brain: The Ramans do everything in threes .
Clarke denied that this sentence was a hint that the story might be continued. In his foreword to the book's sequel, he stated that it was just a good way to end the first book, and that he added it during a final revision.
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