Massachusetts Governor Charlie Baker said "somebody who knew what they were doing" was involved.
The train, which was heading towards central Boston, was carrying 50 people, none of whom were hurt.
The train operator was mildly injured because the train brushed him as it began to move.
Mr Baker told Boston's Herald Radio that officials have not determined whether the tampering was "negligence versus something else".
Officials found that a safety device meant to prevent the rail cars from operating without a driver was altered.
Mr Baker said it was an "isolated" incident.
The Red Line train left its southernmost station early on Thursday morning, travelling north towards Boston for four stops, the Massachusetts Bay Transportation Authority (MBTA) said.
Authorities eventually shut off the train by cutting off power from an electrified third rail.
Fernanda Daly, who was on the train, told the AP News Agency things seemed normal until the lights went on and the train slowed down.
"The people who were on the first car were trying to knock on the door of the conductor and that's when we discovered no one was there," she said.
Karrie Mohammed told the Boston Globe that she and other passengers pushed their way to the front of the train to the conductor's office to find no one was there.
She called the experience "frightening".
Authorities are interviewing passengers who were on the train.
Boston's FBI office is in talks with transit police about the incident.
A Boston subway train which left its station without a driver and travelled to four other stations was tampered with, say officials.