Running performance (RP) and game performance indicators (GPI) are important determinants of success in soccer (football), but there is an evident lack of knowledge about the possible associations between RP and GPI. This study aimed to identify associations between RP and GPI in professional soccer players and to compare RP and GPI among soccer playing positions. One hundred one match performances were observed over the course of half of a season at the highest level of national competition in Croatia. Players (mean ± SD, age: 23.85 ± 2.88 years; body height: 183.05 ± 8.88 cm; body mass: 78.69 ± 7.17 kg) were classified into five playing positions (central defenders (n = 26), full-backs (n = 24), central midfielders (n = 33), wide midfielders (n = 10), and forwards (n = 8). RP, as measured by global positioning system, included the total distance covered, distance covered in five speed categories (walking, jogging, running, high-speed running, and maximal sprinting), total number of accelerations, number of high-intensity accelerations, total number of decelerations, and number of high-intensity decelerations. The GPI were collected by the position-specific performance statistics index (InStat index). The average total distance was 10,298.4 ± 928.7 m, with central defenders having the shortest and central midfielders having the greatest covered distances. The running (r = 0.419, p = 0.03) and high-intensity accelerations (r = 0.493, p = 0.01) were correlated with the InStat index for central defenders. The number of decelerations of full-backs (r = −0.43, p = 0.04) and the distance covered during sprinting of forwards (r = 0.80, p = 0.02) were associated with their GPI obtained by InStat index. The specific correlations between RP and GPI should be considered during the conditioning process in soccer. The soccer training should follow the specific requirements of the playing positions established herein, which will allow players to meet the game demands and to perform successfully.