Yale graduate students who work as teaching and research assistants have filed paperwork to form a union.
A group of student workers from 10 departments filed a petition with the National Labour Relations Board (NLRB) asking to be certified as a union.
The group's leaders said unionising will help them address concerns over pay and benefits.
The move comes one week after the NLRB ruled that graduate assistants at private universities are employees.
That decision gave them the right to unionise under US labour law.
"We are proud to represent the members of Local 33 as they take this historic step forward," said D Taylor, international president of UNITE HERE - the union the students have filed to join.
Yale did not immediately respond to a request for comment.
If the petition is approved, elections would need to be held in each department to confirm support for unionising.
The petition requested the vote to be done in each department separately rather than a single election, a move that could help the pro-union camp.