The Irrawaddy is formed by the confluence of the Nmai (Nmai Hka) and Mali rivers (Mali River). Both branches rise in the glaciers of the high and remote mountains in northern Myanmar in the vicinity of 28° N. The eastern branch, the Nmai, rises in the Languela glacier on the border with Tibet (China) and has the greater volume of water but is virtually unnavigable because of its strong current. The Mali, the western branch, has a gentler gradient and, although interrupted by rapids, has some navigable sections.

About 30 miles (50 km) south of the confluence is Myitkyinā, the northernmost limit of seasonal navigation by the Irrawaddy steamers. Bhamo, about 150 miles (240 km) south of the confluence, is the northern limit for year-round navigation. Between the confluence and Bhamo, the width of the river during the low-water season varies between one-fourth of a mile (400 metres) and half a mile (800 metres). The depth of the main channel averages about 30 feet (9 metres).

Between Myitkyinā and Mandalay, the Irrawaddy flows through three well-marked defiles (narrow passages or gorges). About 40 miles (65 km) downstream from Myitkyinā is the first defile. Below Bhamo the river makes a sharp westward swing, leaving the Bhamo alluvial basin to cut through the limestone rocks of the second defile. This defile is about 300 feet (90 metres) wide at its narrowest and is flanked by vertical cliffs about 200 to 300 feet (60 to 90 metres) high. About 60 miles (100 km) north of Mandalay, at Mogok, the river enters the third defile. Between Katha and Mandalay, the course of the river is remarkably straight, flowing almost due south, except near Kabwet, where a sheet of lava has caused the river to bend sharply westward. Leaving the third defile at Kyaukmyaung, the river follows a broad, open course through the central dry zone—the ancient cultural heartland—where large areas consist of alluvial flats. From Mandalay (formerly the capital of the kingdom of Myanmar) the river makes an abrupt westward turn before curving southwest to unite with the Chindwin River, after which it continues in a southwesterly direction. It is probable that the upper Irrawaddy originally flowed south from Mandalay, discharging its water through the present Sittang River to the Gulf of Martaban, and that its present westward course is geologically recent. Below its confluence with the Chindwin, the Irrawaddy continues to meander through the densely populated dry zone to the vicinity of Yenangyaung, below which it flows generally southward. In its lower course, between Minbu and Prome, it flows through a narrow valley between forest-covered mountain ranges—the ridge of the Arakan (Rakhine) Mountains (Rakhine Mountains) to the west and that of the Pegu Mountains (Bago Mountains) to the east.

The delta of the Irrawaddy begins about 58 miles (93 km) above Hinthada (Henzada) and about 180 miles (290 km) from its curved base, which faces the Andaman Sea. The sides of the delta are formed by the southern extremities of the Pegu Mountains (Bago Mountains) on the east and the Arakan Mountains on the west. The westernmost distributary of the delta is the Bassein (Pathein) River, while the easternmost stream is the Yangon River, on the left bank of which stands Myanmar's capital city, Yangon (Rangoon). Because the Yangon River is only a minor channel, the flow of water is insufficient to prevent Yangon Harbour from silting up, and dredging is necessary. The relief of the delta's landscape is low but not flat. The soils consist of fine silt, which is replenished continuously by fertile alluvium carried downstream by the river. As a result of heavy rainfall and the motion and sediment load of the river, the delta surface extends into the Andaman Sea at a rate of about 165 feet (50 metres) per year.

The lower Irrawaddy River basin has a humid tropical climate, while the upper river basin has a warm humid subtropical climate. Both climatic zones are dominated by the South Asia summer monsoon, which brings the heaviest rains between May and October. At Yangon, in the lower basin, temperatures range from a January mean of 77 °F (25 °C) to an April mean of 86 °F (30 °C); temperatures fall slightly during the summer rainy season. At Myitkyinā, in the upper basin, January temperatures average 64 °F (18 °C), and monthly average temperatures peak at 82 °F (28 °C) in June. Temperatures decrease with altitude up the basin to the glaciated regions where mean annual temperatures are below 68 °F (20 °C). Precipitation varies across the basin from 60 to 100 inches (1,500 to 2,500 mm) per year and falls mainly from May to October.

The volume of the Irrawaddy and its tributaries fluctuates greatly through the year, chiefly because of the character of the monsoon rains, which occur between May and October, but also because of the rapid melting of snow and glaciers during the summer, which adds still further to the volume. The average discharge of the river near the head of the delta varies between a low of 82,000 and a high of 1,152,000 cubic feet (2,300 and 32,600 cubic metres) per second; the annual average discharge is 460,000 cubic feet (13,000 cubic metres) per second. The range between high and low water is also great. Annual variations between low-water level and flood level of 31.7 feet (9.66 metres) and 37.3 feet (11.37 metres) have been recorded at Mandalay and Prome, respectively. The lowest water level occurs in February, and the highest in August. In general, from December to March the river varies between the lowest level and 5 feet (1.5 metres) above it, while from mid-June to mid-October the river is 20 to 30 feet (6 to 9 metres) above the lowest level. The river ports therefore find it necessary to have separate high- and low-water landing points.

The peoples living on the river's banks are culturally diverse. On the upper reaches, the Kachin, who practice shifting agriculture, predominate. In the middle and lower basins, the Burmese are the dominant group, cultivating wheat, cotton, and oilseeds in the central dry zone and rice and jute to the south and in the delta region, where rainfall is more plentiful. Also to the south, and particularly in the delta proper, a considerable minority of Karen and some Indians are to be found among the Burmese majority. In addition, a small number of both rural and urban Chinese are scattered throughout the river's drainage basin.

The main river ports on the Irrawaddy are, from north to south, Myitkyinā, Bhamo, Katha, Mandalay, Myingyan, Chauk, Yenangyaung, Minbu, Magwe, Thayetmyo, Prome (Pyay), Hinthada, and Yandoon. Of these, Mandalay, Chauk, Prome, and Hinthada have good landing facilities. The remaining ports have landing facilities for only one or two barges or lighters, with the vessels mooring alongside the riverbank in most places. Despite Mandalay's position as the chief rail and highway focus in northern Myanmar, a considerable amount of passenger and goods traffic moves by river. The Chindwin valley has no railroad and relies heavily on river transport. Chauk, downstream from the confluence in the oil-field district, is a petroleum port. Like Mandalay to the north and Prome, about 140 miles (225 km) to the south, it is linked to Yangon by road and rail. Hinthada, near the apex of the delta, is the rail junction for lines leading to Kyangin and Bassein (Pathein) (Pathein). A ferry operates between Hinthada on the west bank and the railway station at Tharrawaw on the east bank.

Commercial transportation on the Irrawaddy is maintained for about 800 miles (1,300 km): from Hinthada to Bhamo (670 miles 【1,080 km】) throughout the year but from Bhamo to Myitkyinā (125 miles 【200 km】) for only seven months. More than 2,000 miles (3,200 km) of navigable waterways exist in the Irrawaddy delta. On the Chindwin River, transportation is carried on by steam or diesel vessels throughout the year up to Homalin—about 400 miles (640 km) from its confluence with the Irrawaddy. Seasonal navigation is carried on into Tamanthi, which is 57 river miles (92 km) above Homalin.

The main crossing of the Irrawaddy is the Ava Bridge, which spans the river near Mandalay. Another important bridge crosses the river at Hinthada and connects the western delta with Yangon.

Although the Irrawaddy has been little used for irrigation in the central dry zone, its tributary, the Mu River, has been used for this purpose since the 9th century. The Mu Valley Irrigation Project is among the largest in the country. It permits the dry-season cropping of corn (maize), peanuts (groundnuts), sesame, wheat, cotton, millet, and other dry crops. About one-sixth of the total rice grown in Myanmar comes from the irrigated areas of Mandalay, Sagaing, and Magwe divisions. The river itself also serves to irrigate the delta during the dry season.

As the principal axis of the old Myanmar kingdom, the Irrawaddy River has shaped the country's history, settlement patterns, and economic development. As early as the 6th century, the ancestors of the Burmese arrived from the China-Tibet border area. Using the Irrawaddy as a means of transport, they gradually spread onto the Kyaukse plain and became the major power in the rice-growing region of the north. The Burmese fortified the town of Pagan and eventually gained control over the Irrawaddy and Sittang river valleys and the trade routes between India and China. During the 12th century the town supported a flourishing civilization through rice cultivation and a well-developed network of irrigation canals.

In the 13th century, both the Shan and the Mongols defeated Myanmar armies, and the area dissolved into a number of states, though Burmese kingdoms intermittently reunified the Irrawaddy basin. Beginning in the 16th century, European interests set up trading companies in ports along the coast of Myanmar. By 1886 the British had gained control of Burma (Myanmar) and along with it shipping rights on the Irrawaddy, which also had been sought by the French in an effort to gain a direct route to China.

The British interest was primarily economic, and the opening up of the Irrawaddy delta and the rise of the port of Rangoon (now Yangon) eventually paid off in terms of rice exports. As part of this economic and administrative drive, the British formed the Irrawaddy Flotilla Company in 1865 to convey troops, mail, and stores to riverine stations of British Burma. Starting with four steamers, the company had more than 600 vessels in service by 1940. In 1948 the company was renamed the Inland Water Transport Company. Since then, the service network has declined by half, equipment has become antiquated, and scheduling irregular.