The 40-year-old took over in 2012 and has guided Leigh to the Championship title in each of the past two years.
They won just one game in The Qualifiers in 2015 as they missed out on a place in Super League.
"It is with a heavy heart I have decided to resign as coach," said Rowley in a statement.
"My reasons for leaving are personal and I will not comment further in public or in private."
Paul Rowley has resigned as Leigh Centurions head coach 10 days before the start of the 2016 Championship season.