The five-part documentary series will follow Pilkington as he travels the world alone to "experience how other cultures face up to life's big issues".
The 40-year-old previously hosted Sky1 travel show An Idiot Abroad and was joined by Life's Too Short actor Warwick Davis for the most recent third run.
"I've been on the planet for 40 years now, and I'm still none the wiser as to what it's all about really," said Pilkington.
"I've never worried about life's big questions. People at my age sit about pondering about, 'Why are we here?' - the only time I ever asked meself that is when Suzanne booked us a surprise holiday to Lanzarote."
Sky's head of factual Celia Taylor added: "We are thrilled to be continuing our relationship with Karl following three series of An Idiot Abroad, which all resonated brilliantly with our customers.
"The Moaning of Life will be a unique take on the challenges that we all face in life, presented in Karl's inimitable way."
> An Idiot Abroad returns with 920,000 for Sky1
Watch Karl Pilkington and Warwick Davis discuss the last series of An Idiot Abroad below: