The 45-year-old replaces Grant McCann, who left to take over at Hull last month.
Former West Brom manager Moore played over 80 games for Rovers in the mid-1990s and is delighted to back at the club.
He told Doncaster’s website: “It feels really good to be back, having been here before as a player to be back as the manager is an honour for me.
“I’m looking forward to getting to know everybody around the place, the role really appealed to me given the Club Doncaster model currently in place.”
Chief executive Gavin Baldwin said: “I’m really pleased to have Darren on board, he was a really strong candidate and I’m confident he’s a really good fit for the club.
“His values match ours, and I’m sure our supporters join the owners and myself in giving him a warm welcome and wishing him well at the club.”