NatMags' editorial director, Lindsay Nicholson, will oversee the magazine until a replacement editor is found.
She relaunched with the November issue. It combined coverage of house and garden, cooking, decorating, beauty, travel and health.
Line, a former Homes & Gardens editor, joined NatMags in September 2004 and worked on special projects. He was appointed She editor last June.
Before joining the publisher, he was the chief executive of the Prince's Foundation, where he represented the Prince of Wales' charitable initiatives in art and design.
Line said: "I have enjoyed the time I have spent at NatMags and I feel immensely proud of what we have created in the new She. I always saw this as a project with a finite timescale and, having spent the past two years creating something new, I now feel it is time for me to move on and look for fresh challenges."
She recorded a circulation hike of 5.7 per cent to 156,674 copies in the June to December Audit Bureau of Circulations figures.