John Millman defeated Feliciano Lopez 6–1, 6–3, 4–6, 7–5 in the first round of the Australian Open on hard court on 17 January 2022, confirming his status as pre-match favourite at odds of 1.41 to Lopez's 3.15. Millman controlled the opening two sets with relative ease, breaking down the Spanish veteran's resistance through consistent play. Lopez mounted a response in the third set, forcing a fourth-set decider where Millman ultimately prevailed despite Lopez's late rally. The victory sends Millman through to the second round at Melbourne Park, whilst Lopez's tournament campaign ends in the opening stage.