Sherena Daniels had been in intensive care at the state-run hospital since she was airlifted there early on May 22, the morning after the fire raced through the dorm at a government boarding school in the town of Mahdia, which serves indigenous villages in southwest Guyana.
She died early on Tuesday, the ministry said.
Police say the blaze was deliberately set by one of Daniels' colleagues who became angry after the dormitory matron seized the girl's mobile telephone to prevent her from making contact with older men in the area.
State prosecutors charged the 15-year-old with 19 counts of murder on Monday.
A court remanded her to juvenile detention until July 5, when the state and defence lawyers will decide if they are ready to proceed with a preliminary hearing.
She was not required to enter a plea.
In all, 19 female students and one five-year-old boy have died.
More than two dozen students were injured, most of them aged 12 to 18.
Another critically injured girl is receiving specialist treatment at the Northwell Burn Center at the University Hospital in New York, and her condition is improving, the ministry said.
The dormitory fire outranked what had been the country's deadliest fire in recent times, when 17 inmates were killed at the main Georgetown prison in 2016.
Police alleged that the inmates had set fire to mattresses to protest overcrowding, trial delays and other woes.
More than a dozen others were badly wounded.
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