Following Obafemi's declaration for Ireland, Michael was called up for the senior Ireland squad for the first time in November 2018. In the UEFA Nations League match against Denmark in November 2018, he came on as a substitute in the second half of the 0–0 draw against Denmark to make his debut. He also became the first player born in the 2000s to win a senior cap for Ireland.

Obafemi's form for Swansea City in the Championship saw him earn a recall to the Ireland squad in June 2022 for the UEFA Nations League. Following a substitute appearance in the 1-0 defeat against Ukraine, he started against Scotland and capped off a Man of the Match performance with an incredible long-range effort and an assist in the 3-0 win.