"Domingos Paciencia is no longer the coach of Deportivo," the Galician club, who are bottom of La Liga and lost 3-0 at home to Granada on Saturday, said in a statement on their website.
The club later unveiled Vazquez as Paciencia's replacement on a contract until the end of the season that will be extended by a year if Depor avoid relegation.
Vazquez has wide experience coaching in Spain and has had stints at clubs including Real Mallorca, Real Betis, Rayo Vallecano and Celta Vigo.
Vazquez told a news conference Depor needed to win eight of their remaining 15 games to secure their top-flight status.
"I am arriving at a difficult moment but I am convinced that it's not impossible," he said.
Paciencia, a former Sporting Lisbon coach, was appointed to replace Jose Luis Oltra after he was sacked at the end of December despite leading the club back into the first division after they were relegated in the 2010/11 season.
The Portuguese got off to a promising start with a 1-0 victory at home to Malaga and a 1-1 draw at Real Sociedad but suffered a run of four defeats, culminating in the reverse to fellow strugglers Granada.
Depor have fallen a long way since winning La Liga in 2000 and blazing a trail in Europe and are one of many Spanish clubs who have been forced into administration due to crippling debts.
