The line connects the Tokyo wards of Minato, Shinagawa, Ōta, and the Kanagawa municipalities of Kawasaki, Yokohama and Yokosuka.

The Keihin Railway opened the Kawasaki to Omori section in 1901 as a 1,435 mm (4 ft 8+1⁄2 in) gauge line electrified at 600 V DC.

In 1930, the Shonan Electric Railway opened the Uraga to Koganecho section as a 1,435 mm (4 ft 8+1⁄2 in) gauge line electrified at 1,500 V DC.

Keikyū Kamata Station was rebuilt as a new complex dual level junction to connect the Mainline with the Airport Line.

[3][4][5] Elevation of the section between Shinagawa and Shimbamba, including a rebuilding of the Kitashinagawa station, is underway as of 2023, due to be completed in 2029.

From the start of the revised weekday timetable on 7 December 2015, two Morning Wing limited-stop commuter services from Miurakaigan on the Keikyu Kurihama Line to Shinagawa and Sengakuji in Tokyo were introduced.

Heavy rains caused the mudslide, 7 months after a report by the train company to the Transportation Minister that there was little probability of such an occurrence in that area.

The accident occurred in Yokosuka, and the approximately 100 commuters on board later walked about 200 m to the nearest station to continue their journeys via bus.

[14] On 5 September 2019 at 11:43 am,[15] a rapid limited express (Aoto on the Keisei Oshiage Line to Misakiguchi)[16][17] collided with a truck and derailed at a level crossing between Kanagawa-shimmachi and Nakakido (now; Keikyū Higashi-Kanagawa) Stations in Yokohama's Kanagawa Ward.

[18] According to the police and other reports, Motohashi was driving fruits from Yokohama to Narita and got stuck on the level crossing after attempting a right turn from a narrow side road that was not part of his normal route.