Irish surveyor and cartographer James McCarthy, F.R.G.S., who served as Director-General of the Siamese Government Surveys prior to establishment of the Royal Thai Survey Department, wrote in his account, "Mae Nam is a generic term, mae signifying "mother" and Nam "water," and the epithet Chao P'ia signifies that it is the chief river in the kingdom of Siam.

"[5] Herbert Warington Smyth, who served as Director of the Department of Mines in Siam from 1891 to 1896,[6] refers to it in his book first published in 1898 as "the Mae Nam Chao Phraya".

In Bangkok, the Chao Phraya is a major transportation artery for a network of river buses, cross-river ferries, and water taxis ("longtails").

All of the tributaries, including the lesser khwae, form an extensive tree-like pattern, with branches flowing through nearly every province in central and northern Thailand.

[16] The watershed is divided into the following basins: To the west, the central plain of Thailand is drained by the Mae Klong and the east by the Bang Pakong River.

The lower central plain from the delta north to Ang Thong Province is a flat, low area with an average of two metres above sea level.

Further north and into the plains of the Ping and the Nan the elevation is over 20 m. Then the mountains that are the natural boundary of the Chao Praya watershed form a divide, which has, to some degree, historically isolated Thailand from other Southeast Asian civilisations.

Southern portions of the divide's boundary correspond less to the nation's political border, because isolation in this area was prevented by the ease of transportation along the lowlands surrounding the Gulf of Thailand, allowing a unified Thai civilisation to extend beyond the watershed without issue.

Much of the wildlife that once inhabited these plains has disappeared, including a large number of fish in the river systems, birds such as vultures, the Oriental darter (Anhinga melanogaster), white-eyed river martin (Pseudochelidon sirintarae), the sarus crane (Grus antigone)[18] and animals such as tigers, Asian elephants, Javan rhinoceroses, and the much-hunted Schomburgk's deer.

[20] In general, the aquatic fauna of Chao Phraya and Mae Klong show clear similarities, and they are sometimes combined in a single ecoregion with 328 fish species.

[20] Despite their similarities, there are also differences between the aquatic fauna of Chao Phraya and Mae Klong; the latter (but not the former) is home to a few taxa otherwise only known in major Burmese rivers: the Irrawaddy, Salween, and Tenasserim.

This included the Nan River basin, a tributary of the Chao Phraya, which is home to a number of taxa (for example, Ambastaia nigrolineata and Sectoria) otherwise only known from Mekong.

[31] The critically endangered red-tailed black shark, a small colourful cyprinid that is endemic to Chao Phraya, is commonly seen in the aquarium trade where it is bred in large numbers, but the only remaining wild population is at a single location that covers less than 10 km2 (4 sq mi).

[32] The critically endangered Siamese tigerfish has been entirely exirpated from Chao Phraya and Mae Klong, but small populations remain in the Mekong basin.

[33] Many other species that either are prominent in the aquarium trade or important food fish are native to the Chao Phraya basin, such as the climbing perch, blue panchax, Asian bumblebee catfish, giant snakehead, striped snakehead, walking catfish, banded loach, several Yasuhikotakia loaches, tinfoil barb, Siamese algae eater, silver barb, pearl danio, rainbow shark, Hampala barb, black sharkminnow, Leptobarbus rubripinna, long pectoral-fin minnow, bonylip barb, Jullien's golden carp, blackline rasbora, scissortail rasbora, Tor tambroides, finescale tigerfish, marble goby, Chinese algae eater, giant featherback, clown featherback, giant gourami, several Trichopodus gouramis, iridescent shark, several Pangasius, Belodontichthys truncatus, several Phalacronotus sheatfish, several Wallago catfish, largescale archerfish, smallscale archerfish, and wrestling halfbeak.

Nutrient pollution causes algae to grow faster than ecosystems can handle, harming water quality, food resources for aquatic animals, and marine habitats.

PCD rated water quality at the mouth of Chao Phraya at Bangkok's Bang Khun Thian District as "very poor", worse than in 2014, and their findings indicated large amounts of wastewater were discharged into the river from households, industry, and agriculture.