He served as the President of Eastern Sumi Students Union before entering active politics as a member of the Indian National youth Congress.
While in opposition, he led a campaign for the dismissal of the then state Education Minister, Nyeiwang Konyak who was allegedly involved in financial irregularities of INR 5,000,000 in the department.
He appealed to then Nagaland state governor Nikhil Kumar to accord sanction for prosecution under the Prevention of Corruption Act.
In the closest election in recent history, Yepthomi won a second term in Lok Sabha by a margin of 16344 votes.
In May 2020, the Lok Sabha speaker appointed Yepthomi as an associate member of the Delimitation Commission tasked with redrawing parliamentary and assembly constituencies for Jammu and Kashmir, Assam, Manipur, Arunachal Pradesh, and Nagaland.