Michael Rankine's double sent League One Yeovil tumbling out of the FA Cup.
Rushden went ahead just before the half-hour when captain Chris Hope met a Dave Savage cross to head home.
Rushden doubled their lead after eight minutes of the second half when Rankine pounced to send an unstoppable shot beyond keeper Steve Mildenhall.
Chris Cohen's left-footed shot briefly revived Yeovil's hopes but on 74 minutes Rankine bagged his second with a neat volley following a corner.
606 DEBATE: Give your thoughts on the match
Rushden & D'monds: Tynan, Wilson, Hope, Hatswell, Watson, Berry, Savage, Shaw (Sedgemore 90), Kelly, Tomlin (Jackson 83), Rankine (Chillingworth 87).
Subs Not Used: Eyre, Grainger.
Goals: Hope 28, Rankine 54, 75.
Yeovil: Mildenhall, Lynch, Forbes, Tonkin (Thomas 57), Jones, Davies, Terry, Barry, Cohen, Morris (Welsh 78), Gray (Webb 86).
Subs Not Used: Behcet, Kalala.
Goals: Cohen 62.
Ref: J Singh (Middlesex).