FIFA says number two Samoura leaving job at end of year
Samoura said in a statement she wanted to spend more time with her family.
FIFA President Gianni Infantino hailed the Senegalese as "a trailblazer".
"Her passion and enthusiasm to drive change has been inspirational," Infantino said.
Samoura was also FIFA's first non-European Secretary General.
She said she had intended to announce at a FIFA Council next week that she was stepping down but said she had moved forward her announcement after she became aware of "growing speculation" about her position.
FIFA gave no indication of who would succeed her.
Samoura has divided opinion within the football world, throwing her support behind proposals including a World Cup held every two years that were later discarded.
She has been heavily involved in the planning of this year's Women's World Cup in New Zealand and Australia.
Last month Samoura appealed to broadcasters to return to the negotiating table to avoid a TV blackout of the tournament in major European countries.
Her efforts appear to be bearing fruit as, according to reports in Germany on Wednesday, public networks ZDF and ARD are set to show matches there and French broadcasters are also reportedly close to a deal.
According to information seen by AFP's German sports subsidiary SID, an agreement between FIFA, the networks and the European Broadcasting Union will soon be announced.