Agriculture is the backbone of Pakistan’s economy. Food security depends upon a sustainable agricultural production and higher levels of yield. Wheat is a major cereal crop of Pakistan that severely faced by weed infestation in lowering approximately 45% wheat yield So, controlling weeds is one of the essential requirements of the production system to enhance yield. Use of herbicides can efficiently control weed populations, but such products have environmental and health hazardous effects along with weed resistance problem. Allelopathy is eco-friendly strategy and therefore useful in controlling weeds and to enhance crop productivity. Keeping in view, the present study was conducted to screen out plant extracts of some plant extracts such as Carica papaya, Lantana camara, Pinus roxburghii and Rhazya stricta for the allelopathic activity against major weeds (i.e. Avena fatua, Chenopodium album, Euphorbia helioscopia Phalaris minor and Rumex dentatus) of wheat crop. The current investigation was based on the hypothesis that the allelopathic potential of plants can be an effective weedicidal tool but should not significantly harm the crop of interest. The preliminary screening of the selected plants were carried out on filter paper, soil and agar in the laboratory by using aqueous, hexane and methanolic extracts and sandwich method. Based on preliminary screening and data on germination percentage, radical and plumule length of weeds, it was observed that methanolic extract of L. camara leaf exhibited significant inhibitory effect on all tested weeds, while wheat plants remained unaffected. Three fractions of leaf methanolic extract of L. camara were obtained by using combiflash. Activity guided isolation of these three fractions showed that fraction 2 was found the most active in suppressing all the tested weeds. Assessment 2 of physiological effect on weed species following application of fraction 2 showed that the total chlorophyll contents and protein contents were suppressed significantly in all tested weeds as compared to their respective controls. Superoxide dismutase and peroxidase contents were increased in T3 (50%) and T2 (75%) while in T1 (100%), superoxide dismutase and peroxidase contents were significantly reduced as compared to their respective controls. The NMR and GC-MS analysis of leaf methanolic combiflash fraction 2 exposed four potentially active compounds i.e., Methyl palmitate, Methyl stearate, Methyl oleate and Methyl linoleate. The allelopathic activity of these potentially active compounds (allelochemicals) were explored first time against tested weeds of wheat crop. This is recommended that identified and purified compounds need to be further evaluated regarding their allelopathic potential compared with the standard herbicides available in the market. The same will be tested against a variety of other problematic weeds of various important crops. The cost-effective measurement of these identified compounds with the available products.