Water soluble CdS quantum dots (QDs) have been synthesized using thioglycolic acid (TGA) as surface modifying agent through a one step process by using safe and low cost materials. These TGA capped CdS QDs are highly stable in aqueous solution and applied for ultrasensitive tetracycline (TC) and oxytetracycline (OTC) sensing. The approach was based on the fluorescence of the QDs selectively quenched in the presence of TC and OTC, respectively. Under optimal conditions, the relative fluorescence intensities of CdS QDs were decreased linearly with increasing TC and OTC in the range of 0.05 to 10.0 μM and 0.1 to 10.0 μM, respectively. The limit of detection (S/N = 3) was 5.0 nM for TC and 10.0 nM for OTC, respectively. The RSD for eleven determinations of 5.0 μM TC was 1.26% and 5.0 μM OTC was 0.8%, respectively. There was no significant wavelength shift on the fluorescence-quenched signals in the presence of the drugs. The effect of common foreign substances on the fluorescence of the QDs was examined to evaluate the selectivity and the results showed a high selectivity of the TGA capped CdS QDs towards TC and OTC. The method presented here is simple, rapid, inexpensive, sensitive and suitable for practical application.