Some 17,000 protesters called on Prime Minister Yukio Hatoyama on Sunday to move the controversial facility out of Okinawa, Kyodo news agency reported.
The rally comes just days ahead of a visit to Japan by US Secretary of State Hilary Clinton.
The relocation of the Futenma airbase is at the center of a dispute between Washington and Tokyo.
Hatoyama had promised to move the base off Okinawa by the end of this month. However, local media say the government has abandoned the deadline and is now seeking to settle the feud by November.
The islanders have suggested that the Futenma base should be moved off the island of Okinawa or even outside of Japan altogether.
The Futenma airbase has been used by the US since the final days of World War II. Some 47,000 US troops are currently based in Japan, with more than half of the soldiers stationed in Okinawa.
Hatoyama's failure to move the base will endanger his weakening ruling coalition. The issue has threatened the political future of Hatoyama with both Washington and his political allies putting him under pressure to find a solution to the deadlock.