Chemical exchange saturation transfer (CEST) imaging benefits from a longer saturation duration and a higher saturation duty cycle. Dielectric shading effects occur when the radiofrequency (RF) wavelength approaches the object size. Here, we proposed a simultaneous parallel transmission‐based CEST (pTx‐CEST) sequence to prolongate the saturation duration at a 100% duty cycle and improve the RF saturation homogeneity in CEST imaging. The simultaneous pTx‐CEST sequence was implemented by switching the CEST saturation module from the non‐pTx to pTx mode, using the pTx functionality with both transmit channels being driven simultaneously (instead of time‐interleaved). The optimization of amplitude ratio and phase difference settings between RF channels for best B1 homogeneity was performed in phantoms of two different sizes mimicking the human brain and abdomen. The optimal amplitude and phase settings generating the best B1 homogeneity in the phantoms were used in pTx‐CEST scans of the human study. The comparison of the maximum achievable saturation duration between the non‐pTx‐CEST and pTx‐CEST sequences was performed in a protein phantom, healthy volunteers, and a metastatic brain tumor patient. The optimal amplitude ratio and phase difference setting between transmit channels manifested circular and elliptical polarization in the head‐sized and abdomen‐sized phantoms. In the brain, the maximum saturation durations achieved at a 100% duty cycle using the simultaneous pTx‐CEST sequence were prolonged to 2240, 3220, and 4200 ms compared with 980 ms using the non‐pTx‐CEST sequence at repetition times of 3, 4, and 5 s, respectively. The longer saturation duration helped improve the image contrast between the tumor and the normal tissue in the patient. The optimized elliptical polarization mode saturation pulses yielded improved uniformity of CEST signals acquired from the human abdomen. The proposed simultaneous pTx‐CEST sequence enabled essentially arbitrarily long saturation duration at a 100% duty cycle and helped reduce the dielectric shading effects with the optimized RF setting. A parallel transmission‐based CEST (pTx‐CEST) sequence to extend the maximum saturation duration at 100% duty cycle and mitigate shading effects in CEST imaging. The longer saturation duration provided by the pTx‐CEST sequence helped to improve the tumor‐normal contrast in the patient. The optimized elliptical polarization mode saturation pulses improved the uniformity of CEST signals acquired from the human abdomen.