Tesco's development subsidiary Spenhill has had its revised plans for a £200m scheme in Kirkby town centre approved by Knowsley Council.
As well as a new 146,000 sq ft superstore Tesco plans to build another 90 retail and leisure units.
Tesco's earlier plans were dismissed after a public inquiry in 2009. The scheme was reduced by 40% from 500,700 sq ft to 300,400 sq ft and a proposed stadium for Everton FC removed.
Cllr Dave Lonergan, Knowsley Council's cabinet member for regeneration, economy and skills, said: "This decision is fantastic news for Kirkby and its community, who have been passionately committed to the regeneration of the town for many years. I hope that this approval will be the start of a bright new future for Kirkby – with new jobs, buildings, facilities and opportunities for the whole community to enjoy.
"The council has always been committed to securing the right kind of regeneration in Kirkby and we are confident that these proposals, along with other exciting plans for the town, will bring about the improvements and changes that the people of Kirkby want and more importantly deserve.
"Particularly, we are confident that this project will deliver valuable employment opportunities for local people, at a time when jobs and training are incredibly difficult to find."
The proposals were first submitted for consideration in August 2010.