Background and Purpose: Preclinical studies suggest that highly selective dopamine D3 receptor (D3R) antagonists or partial agonists hold promise for treating substance use disorders (SUD). However, their limited effectiveness in reducing cocaine self-administration is a major drawback. This study investigated whether cariprazine (a D3R-preferring partial agonist) and its analogs ESG-1-60 and ESG-1-61 have enhanced efficacy in reducing cocaine-taking and -seeking behavior. Experimental Approach: In vitro BRET experiments were used to characterize the functional efficacies of cariprazine and its analogs. Intravenous cocaine self-administration and reinstatement models were used to evaluate efficacy in reducing cocaine-taking and -seeking behavior. Optical intracranial self-stimulation (oICSS) procedures assessed effects on DA-dependent behavior. Open-field locomotion, oral sucrose self-administration, and conditioned place-preference were used to evaluate potential unwanted side effects. Key Results: BRET functional assays indicated that cariprazine and ESG-1-60 are D3R-preferring partial agonists, while ESG-1-61 is a D3R-preferring antagonist/inverse agonist. All three compounds inhibited cocaine self-administration under both fixed-ratio and progressive-ratio reinforcement schedules and reduced cocaine-induced reinstatement of drug-seeking behavior in both male and female rats. The compounds did not alter locomotor behavior but suppressed sucrose intake and DA-dependent oICSS. Cariprazine and ESG-1-61 produced significant place aversion, while ESG-1-60 did not. Chronic administration of ESG-1-60 inhibited cocaine self-administration. Conclusions and Implications: Novel D3R-preferring compounds ESG-1-60 and ESG-1-61 are highly effective in reducing cocaine taking and seeking under various reinforcement conditions. ESG-1-60 warrants further investigation as a new pharmacotherapy for treating cocaine use disorder due to its effectiveness in these models and lack of unwanted behavioral effects.