Purpose: To compare the physical demands and performance indicators of male professional cyclists of 2 different categories (Union Cycliste Internationale WorldTour [WT] and ProTeam [PT]) during a cycling grand tour. Methods: A WT team (n = 8, 31.4 [5.4] y) and a PT team (n = 7, 26.9 [3.3] y) that completed “La Vuelta 2020” volunteered to participate. Participants’ power output (PO) was registered, and measures of physical demand and physiological performance (kilojoules spent, training stress score, time spent at different PO bands/zones, and mean maximal PO [MMP] for different exertion durations) were computed. Results: WT achieved a higher final individual position than PT (31 [interquartile range = 33] vs 71 [59], P = .004). WT cyclists showed higher mean PO and kilojoule values than their PT peers and spent more time at high-intensity PO values (>5.25 W·kg−1) and zones (91%–120% of individualized functional threshold power) (Ps < .05). Although no differences were found for MMP values in the overall analysis (P > .05), subanalyses revealed that the between-groups gap increased through the race, with WT cyclists reaching higher MMP values for ≥5-minute efforts in the second and third weeks (Ps < .05). Conclusions: Despite the multifactorial nature of cycling performance, WT cyclists spend more time at high intensities and show higher kilojoules and mean PO than their PT referents during a grand tour. Although the highest MMP values attained during the whole race might not differentiate between WT and PT cyclists, the former achieve higher MMP values as the race progresses.