The present study was based on the hypothesis that mulching materials can directly control weeds and indirectly regulate crop growth and development by improving soil fertility. An experiment was conducted to evaluate the “Comparative efficacy of different mulching materials to enhance growth and development and to control weed infestation in cotton” at Student’s Experimental Farm, Department of Agronomy, Sindh Agriculture University Tandojam Sindh-Pakistan, during Kharif season, 2016, in triplicate with randomized complete block design (RCBD). The net plot size was 4m x 3m (12m-2). There were three cotton varieties (Haridost, Shahbaz, and Sind-1), three mulching materials (wheat straw, sunflower, and banana leaves, each applied at 12 t ha-1), and a control without any mulching treatment. The study revealed that the maximum sympodial branches plant-1 (27.93), opened bolls plant-1 (47.53), weight of seed cotton plant-1 (124.55 g), seed index (8.73 g), seed cotton yield (5394.4 kg ha-1), staple length (30.33 mm), ginning out-turn percentage (37.96%) and oil contents (22.45%) were recorded in Sindh-1 with banana leaves as mulching material. The same treatment caused the maximum leaf area (136.56 cm-2), and leaf area index (4.92 cm) in Haridost. The minimum weed density (55.00 m-2), weed fresh (293.6 g m-2) and dry biomass (122.52 g m-2) with maximum weed control (81%) was recorded with banana leaves as mulching material in Sindh-1. It can be concluded that mulching with banana leaves at 12 t ha-1 significantly reduced the weeds infestation, resulting in enhanced growth, yield, and physiological parameters of the cotton crop.