The aim of this study was to analyze the effects of match location, quality of opposition and match outcome on match running performance according to playing position in a Portuguese professional football team. Twenty-three male professional football players were monitored from eighteen Portuguese Football League matches during the 2019–2020 season. Global positioning system technology (GPS) was used to collect time-motion data. The match running performance was obtained from five playing positions: central defenders (CD), fullbacks (FB), central midfielders (CM), wide midfielders (WM) and forwards (FW). Match running performance was analyzed within specific position and contextual factors using one-way analysis of variance (ANOVA) for repeated measures, standardized (Cohen) differences and smallest worthwhile change. CM and WM players covered significantly greater total distance (F = 15.45, p = 0.000, η² = 0.334) and average speed (F = 12.79, p < 0.001, η² = 0.294). WM and FB players covered higher distances at high-speed running (F = 16.93, p = 0.000, η² = 0.355) and sprinting (F = 13.49; p < 0.001, η² = 0.305). WM players covered the highest number of accelerations (F = 4.69, p < 0.001, η² = 0.132) and decelerations (F = 12.21, p < 0.001, η² = 0.284). The match running performance was influenced by match location (d = 0.06–2.04; CI: −0.42–2.31; SWC = 0.01–1.10), quality of opposition (d = 0.13–2.14; CI: –0.02–2.60; SWC = 0.01–1.55) and match outcome (d = 0.01–2.49; CI: −0.01–2.31; SWC = 0.01–0.35). Contextual factors influenced the match running performance with differential effects between playing positions. This study provides the first report about the contextual influence on match running performance in a Portuguese professional football team. Future research should also integrate tactical and technical key indicators when analyzing the match-related contextual influence on match running performance.