Cotton fibers mainly consist of cellulose biological macromolecule, and its exceedingly flammable nature has severely restricted its application in the fields requiring flame retardancy. To endow cotton fabric with excellent flame retardancy and superior durability, a high-efficiency durable flame retardant (THPO-P) with ammonium phosphate ester and phosphine oxide groups was synthesized and chemically bonded to cotton fabric through padding-baking method. THPO-P showed high flame-retardant efficiency, and the add-on of 5.9% was sufficient to prepare cotton fabric with self-extinguished feature. With the add-on of 19.9%, treated fabric possessed excellent fire safety and durability. The total heat release and peak heat release rate values reduced by 77.1% and 91.8% in contrast to pristine fabric, respectively. Its LOI value still reached up to 33.4% even after 50 laundering cycles, which was far beyond the flame-retardant standard. THPO-P played flame-retardant role by restraining the release of flammable volatiles, liberating nonflammable gases and promoting the char formation during combustion. The flame-retardant treatment deteriorated the tensile strength, whiteness and softness of cotton fabric.