Publisher H Bauer said Jo Checkley was leaving the company to "pursue new interests" and that it had yet to find a replacement.
David Goodchild, managing director of H Bauer, said: "On behalf of the team, I'd like to take this opportunity to thank Jo for her hard work and professionalism throughout her time here at H Bauer.
"During Jo's editorship, That's Life! has remained one of the leading true life magazines in the UK, despite numerous launches into this competitive sector in recent years. We wish Jo every success for the future."
That's Life! recorded a year-on-year fall in sales of 10.7 per cent during the second half of last year.
According to the most recent figures from the Audit Bureau of Circulations the magazine has an average weekly sale of 378,551.
The company said it would begin looking for a new editor in the coming weeks.
Oliver Luft writes for Press Gazette.