The former Ajax, Real Madrid and Netherlands midfielder has been installed, along with assistant Valerio Fiori, until the end of the season at the Riazor.
Seedorf succeeds Cristobal Parralo, who was appointed as interim boss until June when he succeeded Pepe Mel last October.
However, the 5-0 hammering at the hands of Real Sociedad persuaded Deportivo to cut his tenure short after two wins in 13 LaLiga games, with the side languishing third bottom.
Former AC Milan boss Seedorf had a brief spell in charge of Chinese team side Shenzhen in 2016.
He appeared in line for a surprise switch to English football when he was interviewed by League One club Oldham Athletic last year, while a proposed move to Brazil to take charge of Atletico Paranaense failed to materialise.