Tanjong Rhu Road was named after the Casuarina trees that grew along the coast of Kallang and Rochore. Casuarina trees are known as pokok rhu in Malay, Rhu being the Malay name for the Casuarina littoria variety of the tree. Post-war reclamation and construction work along the east coast resulted in the uprooting of the Casuarina trees. It is unknown when the road was named Tanjong Rhu but the word was in use since the 17th century, as it appeared in E.G. de Eredis's 1604 Map of Singapore as Tanjon Ro. Other roads in the area, which connect to Tanjong Rhu Road, are named after Tanjong Rhu as well, such as Tanjong Rhu Place, Tanjong Rhu View and Tanjong Rhu Cross.
The whole of Tanjong Rhu was designated to be a marine yard by Raffles in 1822. The area from Sandy Point at the tip of the spit to Deep Water Point, where Tanjong Katong currently is, was to be developed as a shipbuilding yard. Chinese settlers who dwelled in this area were compensated for their move-out of Tanjong Rhu. One of the pioneers of shipbuilding business was Captain Flint who set up a company in 1822. By the 1860s, many boatyards were established including those owned by George Lyons, Thorneycroft and United Engineers, and Tivendale. With the development of trade, the shipyard industry in Tanjong Rhu expanded, helped further by the congestion at the Singapore River. All the boatyards there had to be cleared and relocated to Tanjong Rhu. The boatyards' workers soon settled with their families in Tanjong Rhu and formed a village. As small shipbuilders made their debut at Tanjong Rhu, the area became more populated. In the early years, there was a single main road linking the yards to the village. Travelling between the city and East Coast was by ferry that plied between Johnston Pier at Colleyer Quay and Tanjong Rhu as roads linking these two points came up only in the 20th century.