Herein, three small molecule (SM)-acceptors (POIT-IC, POIT-IC2F, and POIT-IC4F) are developed by combining the side-chain engineering located on the sp3-hybridized carbon atoms of the fused-ring core and the fluorination of end groups. From ITIC to POIT-IC, POIT-IC2F, and then to POIT-IC4F, the SM-acceptors show gradually broadened absorption spectra, increased maximum extinction coefficient, crystallinity, and electron mobilities due to the synergistic effects of side-chain engineering and fluorination. Compared with nonfluorinated ITIC and POIT-IC, as fluorination broadens the molecular spectra, POIT-IC2F and POIT-IC4F with alkoxyphenyl side chains show less decreased LUMO levels than IT-IC2F and IT-IC4F with alkylphenyl side chains, which are conducive to both higher Voc and Jsc for organic solar cells (OSCs). Combined with polymer donor PM6, the POIT-IC4F-based OSCs achieve a device efficiency of up to 13.8% with a high Voc of 0.91 V and Jsc of 20.9 mA cm−2, which are significantly higher than that of the control OSCs based on ITIC (8.9%), POIT-IC (10.1%), or IT-IC4F (12.2%). An efficiency of 13.8% is one of the highest PCEs reported for the annealing-free OSCs. Our results show that the synergistic effects of side-chain engineering and fluorination on SM-acceptor can simultaneously broaden spectral response and minimize voltage loss of OSCs and ultimately achieve high device efficiency.