Afghanistan have pulled out of the tour because of a clash with the country's preparations for their domestic franchise T20 competition.
"We are disappointed the matches won't proceed in July," said a Cricket Ireland spokesperson.
The two Associate Nations were scheduled to meet at Stormont on 4 July, 7 July and 9 July.
Later this month both Ireland and Afghanistan could be handed Test status by the International Cricket Council.
However, Ireland's form in the run-up to the potentially landmark decision has been poor as they suffered hammerings by England, Bangladesh and New Zealand last month.
The Irish drew a home series in Belfast against the improving Afghans last summer and then played a series of games against them in all formats in India in March.
Afghanistan defeated the Irish 3-2 in a one-day series in Greater Noida before going on to hammer John Bracewell's side by an innings and 172 runs in an Intercontinental Cup game.
Despite Wednesday's news, Cricket Ireland said they would "continue to work" with the Afghanistan Cricket Board to see if the series could be rescheduled.
Ireland's scheduled three-match one-day series against Afghanistan in Belfast next month has been called off.