There always has been at least one man from the United States ranked in the Top 30 each week since the inception of the computer-calculated standings on 23 August 1973.
The Serb, who won his 18th major at the Australian Open in February, insisted his focus now is on surpassing Federer's haul of 20 Grand Slams - a record he shares with Rafael Nadal.
The Italian teenager will face the 20-time Grand Slam winner for the second time, having impressed against Nadal in last year's French Open quarter-finals despite losing in straight sets.
Andy Murray has been out of action since suffering groin pain ahead of the Miami Open in March.
A message from the tournament's official twitter account read: "Novak Djokovic will not be playing in the Mutua Madrid Open. 'Sorry that I won’t be able to travel to Madrid this year and meet all my fans”, said Djokovic. 'It’s been two years already, quite a long time. Hope to see you all next year!'".
Berrettini won previous titles at Gstaad in 2018 and Stuttgart and Budapest, both in 2019.
Serbia Open: World No 1 Novak Djokovic commends Aslan Karatsev's 'bravery' following semi-final defeat
The 28th-ranked Karatsev saved 23 of 28 breakpoints to advance to his second final of the year following a 7-5, 4-6, 6-4 victory, gaining a measure of revenge for his defeat by Djokovic in the last four of the Australian Open.
On whether or not he will be vaccinated to guarantee entry to tournaments, 33-year-old Djokovic refused to commit himself.
Serbia Open: Novak Djokovic bounces back from early Monte Carlo exit by cruising into quarters in home event
It was plain sailing for Djokovic, whose loss to Evans was his first of the season, as he won in only an hour and 10 minutes
Djokovic was among several players to test positive after last year's event, which was held in front of thousands of fans with no social distancing.
World number one Djokovic was broken five times by the Briton in their last-16 clash and suffered his first loss of the year, having won the Australian Open for the ninth time in February.
Monte Carlo Masters: Rafael Nadal 'not worried' about COVID-19 infection after Daniil Medvedev practice
Nadal was not considered a close contact of Medvedev, and therefore not required to quarantine, allowing him to pursue a 12th Monte Carlo title.
Monte Carlo Masters: Stefanos Tsitsipas strolls into last-16; Novak Djokovic to face rising star Jannik Sinner
Tsitsipas, who had been given a bye into the second round, took just one hour and 24 minutes to beat 29th-ranked Russian Karatsev.
Rafa Nadal is aiming for a 12th Masters title in the principality ahead of his pursuit of a 14th French Open success and a record 21st Grand Slam.
Nadal has 71-5 record in Monte Carlo where he has fallen short of the quarter-finals just once - on his debut in 2003 as a 16-year-old.
In sum, no 20-something appears poised to wrest the mantle from the 30-somethings who have dominated the sport for so long.
The 23-time Grand Slam champion joins Roger Federer, Rafael Nadal and Novak Djokovic among the stars to have pulled out of the tournament, which gets under way on Monday with qualifying rounds.
Tsitsipas, who was coming off semi-final appearances at the Australian Open and Rotterdam, was denied a sixth ATP trophy.
The 33-year-old Serbian star won his 18th Grand Slam singles crown and ninth Australian Open singles title last month.
Medvedev, who was beaten by world number one Novak Djokovic in this year's Australian Open final, was elevated to second thanks to his win in the final of the Marseille tournament on Sunday.