Three people in total were injured when a substance was thrown at students and a staff member outside the Westminster Academy school in west London on Monday afternoon.
Officers arrested a 35-year-old man in the early hours of Thursday on suspicion of causing grievous bodily harm. He was taken to a central London police station and remains in custody, Metropolitan Police said in a statement.
"The investigation team has been working tirelessly to piece together the events in which two young victims, aged 16 and 14, were approached outside the school by a lone man who threw a substance at them before fleeing," said Detective Superintendent Scott Ware.
The 14-year-old girl sustained serious injuries and "it may still be some time before we know the true extent of how serious her injuries are, but at this time they are being treated as potentially life-changing," he added.
The 16-year-old boy and a 27-year-old woman were discharged from hospital and their injuries are not believed to be life-changing.
Numera Anwar, the school's principal, said a student, a teacher and a member of the public were injured in the "distressing incident" involving an "acid-like corrosive substance".
It occurred on the road outside the school building when students and staff were leaving, she noted.
Britain has battled back against attacks involving corrosive substances such as acid after they spiked in the middle of the last decade, and saw incidents decline until a resurgence in 2022.
The attacks returned to the spotlight this year after an attack on a woman and her two young daughters in London.