He tweeted his farewell to the Railways Ministry, which has been plagued by train accidents over the past few months.
"Thanks to all 13 Lacs+ rail family for their support, love, goodwill. I will always cherish these memories with me. Wishing you all a great life," said Mr Prabhu.
Mr Prabhu, who had met Prime Minister Narendra Modi and offered to resign after the train accidents last month, had been absent from his Rail Bhavan office from August 23.
Mr Prabhu also welcomed Piyush Goyal who will take charge of the Rail Ministry after him.
In his tweets, he congratulated the new ministers as well as those who had been elevated.13 coaches of a train derailed near Muzaffarnagar, Uttar Pradesh. Four days later, 10 coaches of the Kaifiyat Express heading towards Delhi collided with a dumper in Auraiya district, Uttar Pradesh.
Mr Prabhu has also not attended any function as rail minister since then, though he was present at a recent rally in Goa as a BJP MP and a party event.