A field study was conducted in 2002, 2003, and 2004 to evaluate various pre-emergence herbicides (ethafluralin & clomazone, ethafluralin & clomazone + halosulfuron, and ethafluralin & clomazone + imazamox) with or without a winter rye (Secale cereale L.) cover crop in tillage and no-tillage `Appalachian' pumpkin (Cucurbita pepo L.) production. All herbicides were applied within two days of seeding, and no injury was observed with any of the herbicides evaluated at any time during the three growing seasons. Early- and late-season control of all weed species [giant foxtail (Setaria faberi Herrm.), common cocklebur (Xanthium strumarium L.), redroot pigweed (Amaranthus retroflexus L.), and common waterhemp (Amaranthus rudis Sauer)] were highly correlated (0.47 ≤ r ≥ 0.86, P ≤ 0.01) with pumpkin yield and fruit size. The winter rye + no-tillage system provided greater weed control compared to the tillage systems and the no cover crop + no-tillage production system. Although winter rye alone had little influence on pumpkin yield, the no-tillage system improved pumpkin yield and fruit size compared to the tillage system. The two herbicide combinations (ethafluralin & clomazone + halosulfuron and ethafluralin & clomazone + imazamox) improved weed control and pumpkin yields compared to only ethafluralin & clomazone. Although this study indicated that the use of a high-residue winter rye cover crop in no-tillage pumpkin production will provide some weed control, the choice of pre-emergence herbicides is critical to maximize pumpkin productivity. No-tillage pumpkin production is feasible with proper herbicide use and timing, although current herbicide options will not provide optimal weed control.