There was minimal pageantry as the college sweethearts, who wed last month, left from Tokyo airport on Sunday morning.
They will rent an apartment in New York where Mr Komuro works at a law firm.
Under Japanese law, female imperial family members forfeit their status upon marriage to a “commoner”.
The pair were heavily guarded by police and airport security as they strolled through the departure terminal. They passed about 100 journalists who were there to witness them leave, but did not respond to questions.
Their move to New York had long been rumoured and Mako, who took her husband’s name when they got married, is reportedly expected to find a job in the city.
However, the couple faced a set-back to their plans last month when Japanese media reported that Mr Komuro had failed the New York state bar exam. Prospective lawyers have to pass the tests to practise law in the state.
Mr Komuro is currently working as a legal clerk.
The move to the US has drawn comparisons with British royals Meghan Markle and Prince Harry, earning the newlyweds the nickname “Japan’s Harry and Meghan”.
The couple faced significant opposition when they first announced their engagement four years ago and their relationship has been subject to tabloid gossip and controversy over claims that Mr Komuro’s mother had reportedly taken a loan from her ex-fiancé and not paid him back.
The coverage led to the then-princess developing post-traumatic stress disorder, according to the Imperial Household.
When the couple married last month they skipped the usual rites of a royal wedding and turned down a payment offered to royal women upon their departure from the family.
Former princess Mako, who is the niece of Emperor Naruhito, is the first female member of the royal family to decline both.