The recently-merged betting firm said that Mr McCue — who has been with Paddy Power since 2006, and took over from Patrick Kennedy as its chief executive at the start of last year — will cease to be a director of the group as of the end of April.
“I leave Paddy Power-Betfair following the completion of the merger and in the knowledge that this combination will be greater than the sum of its parts,” Mr McCue said in a statement.
“I feel now is the right time to pursue new opportunities,” he added.
It is understood that Mr McCue’s decision was taken very recently and it is not known what his plans are.
Elsewhere, leading UK betting firm William Hill warned yesterday that it now expects full-year operating profits to be lower than last year.
It expects 2016 operating profits to be in the range of £260m to £280m (€328m-€354m) compared to £291.4m last year.
The company is also in advanced discussions to invest in gaming software firm Openbet.
Profit at William Hill’s online segment, which contributes about 35% to overall revenue, is seen lower by £20m-£25m, the company said.
It added that measures to reduce the amount of time spent by punters online had an impact on its online business, while the worst Cheltenham festival in history led to lower-than-expected gross win margins.