Wrexham slumped to their third straight defeat after a Derek Holmes brace and Marc Newsham's strike earned Rotherham their fourth win in five league games.
The Dragons had to play 76 minutes with 10 men after Matt Crowell was sent off for a reckless challenge on Ian Ross.
Holmes opened the scoring after 40 minutes and then made the most of a defensive mix-up to double the lead.
Newsham made sure of the points eight minutes from time after finding himself free in the box to fire home.
Rotherham: Warrington, Joseph, Sharps, Coughlan, Brogan, Taylor (Newsham 70), O'Grady, Danny Harrison (Tonge 44), Ross, Mills, Derek Holmes (Yates 86).
Subs Not Used: Oxley, Todd.
Booked: Sharps.
Goals: Derek Holmes 40, 72, Newsham 82.
Wrexham: Anthony Williams, Baynes, Hope, Steve Evans, Valentine, Aiston, Mark Jones (Johnson 79), Crowell, Llewellyn, Roberts, Proctor.
Subs Not Used: Michael Jones, Pejic, Gareth Evans, Mike Williams.
Sent Off: Crowell (14).
Booked: Llewellyn, Steve Evans.
Att: 3,773
Ref: Gavin Ward (Surrey).
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