Jim Savage, Mando's former head of front-end development, and Sam Birch, its former senior front-end developer, say they want to focus on smaller projects with their own company as Mando continues its push to win larger accounts.
The new firm will focus on front-end development - the code behind the design work users see when they visit websites.
Mr Birch and Mr Savage both spent more than ten years at Mando - and worked together for so long they became collectively known as Jam.
Among their projects was a programme called Google Drive, which hit the headlines in publications from the Liverpool Echo to the Wall Street Journal. It allowed users to drive a virtual car around any city in the world by clicking on internet search engine Google's maps application.
Mr Savage said: "Our time at Mando Group was immensely enjoyable and after contributing to Mando's growing success we now feel the time is right to run our own business.
"With Mando's continuing and successful push into more technology-led enterprise markets, we still feel there is a strong need for a smaller and more reactive approach to user-centric design, particularly in areas of front-end development."
Mr Savage and Mr Birch are now developing an iPad project for an American company specialising in facial recognition software - and also plan to work on joint projects with other North West agencies, including Mando.
Mr Savage said: "Working collaboratively with other like-minded people is something that excites us greatly."
Last month LDP Creative reported that Mando designers Martin Chapman Fromm and Andy Wilkinson had left Mando to form digital brand design company Error.
Mr Chapman Fromm said he wanted Error to start collaborating with other "like-minded organisations" to win contracts and deliver projects.
He said: "We want Error to be about the design and communication work and rely on technology and specialist partners to help deliver projects.
"Being small and agile and being able to flex in different ways per project excites us greatly. There's so much specialist talent in our industry, it makes sense when looking to produce quality work."
Error, based in the city centre, is now working on projects including a "significant financial regulations application used by major financial institutions" and iPhone-related work for a restaurant chain.
Mr Chapman Fromm said he and Mr Wilkinson felt the time was right to set up their own firm.
He said: "We've enjoyed our time at Mando Group, we've played our part in the growth of the company over the last five and nine years respectively.
"The time was right to venture out once more and run our own business.
"Our aim will be to develop a small outfit that builds long-term partnerships with wonderful clients - clients who are interested in the skills we've acquired over the years to help evolve their brand through digital means and look for a bit of spark and imagination in their communications."