The world number 10 hit 28 unforced errors, five double faults and won just four of 21 points behind his second serve in a dismal showing.
Medvedev has become infamous for his outbursts – most notably at last year’s US Open, where he had a meltdown after a photographer walked on court mid-match.
Afterwards, Berrettini wrote ‘scusa Carlo’ on the camera lens – an apology to Italian actor Carlo Verdone, who called Medvedev his favourite player earlier this week.
Wildcard Berrettini, the 2021 Wimbledon finalist making his way back up the rankings after a lengthy injury lay-off, said it was “one of the best performances of my life”.
“I think I missed three shots in the entire match,” Berrettini, 29, said.
“I think the game plan was perfect and my weapons were working.”
Former world number six Berrettini will face rising Brazil star Joao Fonseca next.
World number 15 Andrey Rublev also suffered an early exit, losing 6-4 6-1 to Belgium’s Zizou Bergs.
