Moore returns to the Millers hot seat for a second time after a highly-successful spell between 1997 and 2005 and replaces the departed Robins - who Moore brought to the club in 2000.
The 56-year-old, who has been out of work since being sacked at Tranmere in June, signs a three-year deal at Don Valley Stadium and inherits a squad that sits third in the league and has been widely tipped to earn League Two promotion this term.
"It's just like coming home, that's the feeling I have got for the place. I have always loved Rotherham through good times and bad times and the support I have had from them has been fantastic," said Moore.
"We know what we've done in the past, but that is the past. People say never go back. I think this club is on the up and I believe that I am the man (to take them forward)."