Mixed martial arts (MMA) is a combat sport where competitors utilize strikes (punches, kicks, knees, and elbows) and submission techniques to defeat opponents in a cage or ring. The aim of this study was to investigate the effect of acute caffeine ingestion on punching performance by professional MMA athletes. The study used a double-blind, counterbalanced, crossover design. Eleven professional MMA competitors (27.6 ± 4.3 years and 83.5 ± 7.8 kg of body weight) ingested a dose of caffeine (5 mg·kg−1) or placebo 60 min prior to three sets of punching. Each set consisted of 15 s, at which participants were asked to perform straight punches with maximum strength and frequency with his dominant arm. After each set, a 45 s recovery time was applied. Using a force transducer attached to a cushioned plate, the punch frequency, and mean and maximal punch force was measured. The readiness to invest in both physical (RTIPE) and mental (RTIME) effort was assessed prior to the protocol, and the rating of perceived exertion (RPE) was recorded after. Caffeine ingestion did not result in increased punching frequency, mean and maximum punch force, RTIPE, RTIME, and RPE when compared to the placebo condition. Based on these results, acute caffeine ingestion did not improve punching performance in professional MMA athletes.