She was behind Microsoft boss Satya Nadella.
Gaines was praised for managing the company through a period of volatility.
She was the only Australian and only mining company boss to make the list of 20 global company leaders.
Since being appointed CEO of the iron ore miner in February 2018, FMG has delivered a total return of 90% versus only 5% for the broader ASX 200.
Fortune acknowledged some of FMG's success was attributed to high iron ore prices, but also pointed to the introduction of a higher grade iron product, West Pilbara Fines, and the company's continued investment in technology.
The magazine noted since Gaines' arrival at FMG (first as chief financial officer in 2013), the company's net debt has fallen from $10.5 billion to just $500 million.
Gaines was runner-up in the MNN Awards CEO of the Year earlier this year.
Gaines also topped the list of best-performing CEOs in the Australian Financial Review's annual CEO pay survey, released on Monday.