Smith leaves Dens Park with immediate effect after the news was confirmed on the club's website.
A short statement read: "Dundee FC today announced that they have parted company with manager Barry Smith with immediate effect.
"Until matters regarding this have been formally concluded, no further statement will be made."
Dundee are 15 points adrift at the bottom of the table and look set for a quick return to the Irn-Bru First Division.
The Dark Blues were late additions to the top flight in the summer, after replacing Rangers, and have struggled to compete throughout the campaign.
Smith's future at Dundee came under scrutiny in early January, with reports suggesting his position would be discussed by the club's directors.
He then appeared to receive the backing of the board, who acknowledged the difficult task he has faced this term, while vowing to boost their survival bid by adding new players before the transfer deadline.
David Morgan was signed on loan from Nottingham Forest and former fans' favourite Gary Harkins also returned to Dens Park.
But results failed to improve and the SPL strugglers have not registered a single victory in their last 12 league outings.
Club chiefs now begin the search for a new manager, with Dundee facing a daunting trip to Celtic Park to face the league leaders on Sunday.