The 49-year-old's first senior coaching role came with the Madrid club and he is back at the helm of the Liga club 10 years after leaving Coliseum Alfonso Perez.
Sanchez Flores has been out of work since being sacked by United Arab Emirates outfit Al Ain in March last year, but resumes his coaching career in his home city.
The former Valencia coach takes over from Contra, who left Getafe to take charge of Chinese club Guangzhou R and F.
Romanian Contra revealed last month that Getafe had agreed a compensation package with Guangzhou that would give them much-needed funds and his final game in charge ended in a 2-1 defeat to Rayo Vallecano on Sunday.
Sanchez Flores took his first training session on Monday and later spoke of his delight to be back at Getafe.
"It's a wonderful experience, I am very happy to go home," he said. "I found a club that has grown but still with the same people who continue with the same humility.
"Getafe is always my home, and why show me so happy."
When asked if he considered it a risk to take the role, he replied: "Risky? There is always risk at these levels, I was eager to return to the Spanish league and that is best done in Getafe .
"My priority is to be in Getafe , and so I thought very little when I was told, I soon decided anything."
Getafe are 14th in La Liga, just four points better off than third-bottom Grenada, who have a game in hand.
