It is bounded by (from north clockwise): Lam Luk Ka district of Pathum Thani province; Khlong Sam Wa, Bang Khen and Don Mueang of Bangkok.

Sai Mai was the name of a muban (village) in tambon (sub-district) Khu Khot, Lam Luk Ka District, Pathum Thani Province.

Due to the growth of population in the area, Sai Mai was elevated to district status effective 21 November 1997 to improve service and administration.

Khlong Lat Phrao is one of nine canals in Bangkok that drains rainwater flowing into the city from northern Thailand, but it has been neglected for decades and clogged with refuse.

There are three BTS Skytrain Sukhumvit line stations in Sai Mai: Bhumibol Adulyadej Hospital, Royal Thai Air Force Museum, and Yaek Kor Por Aor.