The ultimate source of the river is at the end of the Makarora River, close to the saddle of the Haast Pass, which flows into the northern end of Lake Wanaka. The southern end of the lake drains into the nascent Clutha close to Albert Town, where it is met by its first main tributary, the Hawea River the outflow of Lake Wanaka's twin, Lake Hawea. It is also met here by the Cardrona River. Shortly thereafter the river widens into Lake Dunstan, an artificial lake created behind the massive hydroelectric dam at Clyde. At this point it is joined by another tributary, the Lindis.
Fifty kilometres south of Lake Wanaka, the Clutha reaches the town of Cromwell, which was substantially altered when the Clyde Dam project was completed in the late 1980s. Here the river is joined by the waters of the Kawarau, which flows from Lake Wakatipu. Prior to the construction of the Clyde Dam, this junction was renowned for the difference in colour between the two rivers’ waters.
The river then flows southeast through the scenic Cromwell Gorge to Clyde and nearby Alexandra, where it is joined by the waters of the Manuherikia River. South of Alexandra the river widens again to form Lake Roxburgh, another artificial lake, behind the Roxburgh Dam, which was constructed in the late 1950s. The town of Roxburgh sits close to the river, 120 kilometres downstream from Lake Wanaka.
From here the river continues southeast past the towns of Ettrick, Millers Flat, and Beaumont, before it is met by the Tuapeka River at Tuapeka Mouth. At this point the river turns southward, before being met by its last major tributary, the Pomahaka River, which joins the Clutha 30 kilometres from the coast. The river passes the town of Balclutha before widening into the Clutha delta which contains the large flat island of Inch Clutha.
The Clutha's average discharge estimated at 570 m³/s, comparable to many much larger rivers. This heavy flow, combined with the relatively small size of the river in global terms, makes the Clutha notoriously fast-flowing, and it is often listed as one of the world's most swiftly flowing rivers, alongside Australia's Macleay and Fitzroy Rivers, the Amazon and Atrato Rivers in South America, and the Teesta River in the Himalayas.
By Christmas 1861, 14,000 prospectors were on the Tuapeka and Waipori fields. The gold rush was short-lived, with most of the alluvial gold played out by 1863, but prospectors continued to arrive, swelling to a maximum of 18,000 miners in February 1864.
The 1978 flood, in which rivers from the Oreti in the south to the Tokomairiro in the north breached their banks, led to the inundation of over 12,000 hectares of land and the loss of over 21,000 livestock. Towns and areas affected stretched from Makarora in the north to Invercargill in the south. The town of Wyndham was completely evacuated, and the towns of Balclutha, Milton and Mataura were seriously affected with many residents moved. The small settlement of Kelso on the banks of the Pomahaka River was completely abandoned and was not rebuilt once the waters subsided. At its peak, at 6.00 a.m. on the 15th, the Clutha's flow was measured at just over 4500 m³/s.
The Clutha also provides irrigation for stone fruit orchards around Cromwell, Alexandra, and Roxburgh, which provide apples, apricots, nectarines, cherries, and peaches. Several small vineyards are also found in the upper reaches of the river.
The spectacular scenery of Central Otago makes the upper Clutha a popular holiday destination, especially for adventure tourism. Jetboating, waterskiing, bungy jumping and parapenting facilities are all to be found close to the river, and Lake Dunstan is also an important rowing venue. Several major ski courses are found close to the river. Curling is also played close to the Clutha in the harsh Central Otago winters.