Tsitsipas strolls into Monte Carlo last 16, Djokovic to face rising star Sinner
Greek Tsitsipas, who had been given a bye into the second round, took just one hour and 24 minutes to beat 29th-ranked Russian Karatsev.
The 22-year-old exploited a whopping 32 unforced errors from Karatsev to set up a clash with either Australian John Millman or Chile's Cristian Garin.
Teenager Sinner has risen to 22nd in the world rankings after reaching the final of the Miami Open earlier this month.
Earlier on Tuesday Daniil Medvedev pulled out of the tournament after testing positive for Covid-19.
World number two Medvedev tested positive on Monday having practised with Rafael Nadal the day before.
Organisers, contacted by AFP, declined to comment on whether third seed Nadal risked being identified as a 'close contact' of Medvedev and forced to quarantine.