Relegated Lewes won their second Blue Square Premier game in a row as Weymouth continued their dismal run.
Lewes keeper Rikki Banks somehow tipped Cliff Akurang's shot over the bar and then kept out Stephen Reed's penalty after Anthony Barness fouled Akurang.
The home side were restricted to long-range shots until Chris Breach nodded home their winner after the break.
Weymouth pushed forward but struggled to create further chances and had Marcus Browning sent off late on.
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