Depor announced the decision on Monday morning in the wake of Saturday's 3-0 home loss to Granada, a defeat which left the Galician club two points adrift at the foot of the Primera Division standings.
A statement on the club's official website read: "The Portuguese coach Domingos Paciencia and his backroom team will no longer be in charge of the first team."
Domingos was appointed on December 30 as the replacement for Jose Luis Oltra, who was dismissed with the club bottom of the standings with just two wins from 17 games.
The 44-year-old Domingos enjoyed an impressive start to life at the Riazor with a victory over high-flying Malaga in his first match in charge and then following that up with a 1-1 draw from their trip to Real Sociedad.
However, Depor have lost all four matches since then, including defeats to relegation rivals Osasuna and Granada.
This weekend's loss to Granada proved the final straw, with Depor now six points adrift of safety and looking in serious danger of an immediate return to the Segunda Division following their promotion last year.
Fitness coach Jose Angel Franganillo took charge of Monday morning's training session as Depor search for a permanent successor to Domingos.
Whoever does take the reins faces a baptism of fire in the hotseat with four of Depor's next five matches pitting them against Sevilla, Real Madrid, Barcelona and arch-rivals Celta Vigo.
Their next fixture is away to Sevilla on Friday night.