The Italian 32nd seed was beaten 4-6, 6-2, 6-4, 5-7, 6-3 in three hours and seven minutes on Court Three.
Berrettini reached the Wimbledon title match in 2021 before losing to Novak Djokovic.
That remains the 29-year-old's only Grand Slam final.
And his limp Wimbledon loss at the hands of 109th-ranked Majchrzak means Berrettini has failed to get past the second round in his past five Grand Slam appearances.