—This contribution proposes a novel time-domain synchronous frequency division multiple access (TDS-FDMA) scheme to support multi-user uplink application. A unified frame structure for both single-carrier and multi-carrier transmissions and the corresponding low-complexity receiver design are derived. Compared with standard cyclic prefix based orthogonal frequency division multiple access systems, the proposed TDSFDMA scheme improves the spectral efficiency by about 5% to 10% as well as imposes a similarly low computational complexity, while obtaining a slightly better bit error rate performance over Rayleigh fading channels.