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Individuals with Down Syndrome exhibit deficits in muscle strength and cardiovascular adaptation, which limit athletic performance. We compared a maximum-intensity 50 m front crawl test between competitive male swimmers with Down Syndrome (SDS; n = 11; 26.5 ± 5.6 years; m ± SD) and a control group of swimmers (CNT; n = 11; 27.1 ± 4.0 years) with similar training routines (about 5 h/week). Wearable sternal sensors measured their heart rate and 3D accelerometry. The regularity index Sample Entropy (SampEn) was calculated using the X component of acceleration. The total times (SDS: 58.91 ± 13.68 s; CNT: 32.55 ± 3.70 s) and stroke counts (SDS: 66.1 ± 9.6; CNT: 51.4 ± 7.4) were significantly higher in the SDS group (p < 0.01). The heart rate was lower in the SDS group during immediate (SDS: 129 ± 15 bpm; CNT: 172 ± 11 bpm) and delayed recovery (30 s, SDS: 104 ± 23 bpm; CNT: 145 ± 21 bpm; 60 s, SDS: 79 ± 27 bpm; CNT: 114 ± 27 bpm) (p < 0.01 for all the comparisons). The SampEn of sternal acceleration showed no differences between the groups and between 0–25 m and 25–50 m. Body pitch correlated strongly with performance in the SDSs (R2 = 0.632, p < 0.01), but during the first 25 m only. The high-intensity front crawl performances differed between the SDS and CNT athletes in terms of time, biomechanics, and training adaptation, suggesting the need for tailored training to improve swimming efficiency in SDSs.