Two penalties by Worthing's Gary Young proved a knock-out blow for Lewes in a battle of the Sussex heavyweights.
The Rebels' captain struck from the spot after 56 and 81 minutes to give Barry Lloyd's side a deserved win at the Dripping Pan.
After an evenly-fought opening, Worthing twice went close to making a breakthrough around the 20 minute mark.
First, Rebels midfielder Steve Sargent tested Russell Tanner with a 25-yard drive which the Rooks keeper held low down.
Then Tanner tipped over a stronger shot by Mark Knee from similar range.
Lewes had threatened little to this point, but Rebels defender Tom Graves almost presented the home side with a gift wrapped opener.
Graves miscued Gareth Green's left-wing cross, creating a chance for Tony Reid which the striker was just unable to snap up at the far post.
Lee Newman turned Graves and beat the defender for pace, only to see his 15-yard shot blocked by Matthew May's legs.
Lewes' Junior Kamara talked himself into the book soon after the break and had more to complain about when Worthing went in front after 56 minutes.
Wesley Lopez cut into the area from the left and was brought down by Danny Davis for a clear cut penalty, which Young converted.
Rooks boss Jimmy Quinn immediately responded by making a double change, replacing Reid and Newman with Ross Venables and Germain Amanuel.
The two substitutes soon teamed up, Venables creating a chance for Amanuel only for May to prevent an equaliser.
Lewes' third sub, Jon Palmer, almost made a dramatic impact twice within three minutes of his introduction, but May was out quickly to block and Palmer put another effort wide.
Worthing doubled their advantage with another Young penalty nine minutes from time after a foul by Marc Cable on Knee.
Cable was thwarted at the other end when May somehow kept out his point-blank shot.
Lewes: Tanner, Davis, Curnow (Palmer 72), Kennett, Chin, Cable, Gedling, Kamara, Reid (Venables 57), Newman (Amanuel 57), Green. Subs not used: Hack, Standen Worthing: May, Young, Hibberd, Walker, Graves, Beech, Carrington, Knee, Alexander (Mateos 83), Sargent, Lopez. Subs not used: Best, Brown, Lewis, Stevens.
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