Donald Trump branded Sadiq Khan "a disaster" and demanded that the London mayor was replaced after three men were killed in separate attacks.
Two teenagers were murdered within minutes of each other in different parts of the capital on Friday, while a man was stabbed to death on Saturday afternoon.
Retweeting a post by right-wing commentator Katie Hopkins about the killings, the president said the English capital needed a new mayor "ASAP".
Trump tweeted: "LONDON needs a new mayor ASAP.
"Khan is a disaster - will only get worse!"
The original post by Hopkins called the capital "Stab-City" and "Khan's Londonistan" alongside two screenshots of BBC News articles detailing the violence.
She wrote: "20 hours in Stab-City UPDATE 2 stabbed to death 1 shot dead Three stabbed - but not dead. Wandsworth & Tower Hamlets This is Khan's Londonistan."
The US president and London mayor have clashed in the past, including on Trump's state visit at the start of June.
Trump branded the mayor a "stone cold loser" in a two-part tweet as he touched down in Britain on June 3.
The Labour mayor then accused the president of "playground behaviour" and claimed he was a "poster boy" for the far-right.
An 18-year-old boy was stabbed to death in Wandsworth on Friday afternoon, minutes before another 19-year-old man was fatally shot in Plumstead.
Just hours later, a man in his 30s was killed in Tower Hamlets, east London.
Three men were also stabbed in a separate attack in Clapham during a weekend of violence in the English capital.
The Metropolitan Police said 14 people - including several boys and a girl - have been arrested in connection with the incidents in Wandsworth, Plumstead and Clapham.
