Almost 3,000 cases were diagnosed in the capital out of a total of 5,042 in the country in 2015, figures from Public Health England (PHE) show.
Since 2010 the number of cases among Londoners has risen by 163%, with 90% of those reported in 2015 among men who have sex with men.
PHE said people were "putting themselves at risk through unsafe sex".
Syphilis is a bacterial infection that initially causes highly infectious sores but can go on to cause serious conditions such as heart problems.
In most circumstances it can be treated with antibiotics but in extreme cases, the sexually transmitted infection can prove fatal.
2,811
cases in the capital in 2015
2,406 cases recorded among men who have sex with men (MSM)
36 median age of MSM diagnosed
74% of MSM diagnosed were white
44% of MSM diagnosed were born in the UK
There are about 54.7m people living in England, 8.7m of which live in London according to the Office of National Statistics.
In 2015, syphilis was diagnosed in all London local authorities with the highest numbers in Lambeth, Southwark, Tower Hamlets and Westminster.
The number of cases among heterosexual men and women has risen slightly but there was a much larger increase among men who have sex with men.
The group, which represents about 2% of the total London population, accounted for 2,406 of 2,811 cases in the capital.
Dr Yvonne Doyle, regional director for PHE London, said it was "worrying to see such alarming rises in syphilis year on year".
She said: "We are seeing large increases in cases of syphilis among men who have sex with men and they now represent 90% of syphilis cases in London.
"Although diagnoses among heterosexuals in the capital are more stable they too continue to be higher than we would like given the effective preventative measures in place."
She called on people to practise safe sex, "including using condoms, regularly being tested and avoiding overlapping sexual relationships".
Nearly 60% of all syphilis cases reported in England were in London, it has been revealed.