Sadiq Khan is flying to New York for four days to attend a series of events including an international climate conference.
The mayor of London is expected to speak at the United Nations climate ambition summit on Wednesday.
He will also use the visit to meet representatives from US businesses and investors looking at London.
His trip takes place three weeks after the controversial expansion of the Ultra Low Emission Zone (Ulez).
What Mr Khan says about the zone to his American audience will be watched closely.
The mayor said he was "honoured" to have been invited to attend the UN climate summit.
He is booked to appear on a number of US TV shows, as well as attending a New York "climate week" event and a discussion on social media at Colombia University.
Mr Khan currently chairs the C40 network of global city mayors, which shares ideas and expertise on tackling climate change. The organisation is funding his visit.
He will preside over a meeting of the C40 steering committee which city mayors who have not travelled to New York will join remotely.
These private sessions are usually a chance for mayors to update colleagues on their progress in tackling environmental challenges and Mr Khan is expected to give an assessment of Ulez.
The other mayors are likely to be fully briefed on the criticisms and political difficulties he has faced.
A spokesperson for City Hall said that the trip will also be a chance to encourage more Americans to visit the capital this autumn.
"I am determined for London to continue being a world leader in tackling the twin dangers of air pollution and the climate emergency, so that we can deliver a brighter future," Mr Khan said.
"My visit to the UN is an opportunity to learn from other cities and nations and ensure London remains at the forefront of global action."