Bill started his hockey career in the 1939-40 season with the Winnipeg Monarchs in the Winnipeg City Junior League, where he recorded just over a point per game. In the 1940-41 season he played for the Providence Reds of the AHL and the Kansas City Americans of the AHA. In the 1941-42 season Mosienko was called up to the Chicago Black Hawks, and there he remained for his entire NHL career.

On February 9, 1942, he scored his first two NHL goals, in the span of 21 seconds. As has already been written, the span of 21 seconds is very important to Bill. Mosienko finished the season back with the Kansas City Americans and spent the next season playing only 10 games, 2 with the Black Hawks and 8 with the Quebec Aces of the Quebec Senior Hockey League.

The 1943-44 season was the first full season Bill played for the Black Hawks, and in terms of point production this was the best year of his career as he netted 32 goals and 38 assists for 70 points, which put him in the top 10 in scoring for that season. Mosienko was known for his skating ability and was ranked as the fastest skater in the NHL. He earned that title by beating the fastest skaters from the other 5 teams in 1950 during a skating contest at the Montreal Forum. He was also ranked as the fastest skater by a poll of sportscaster in all 6 NHL cities. During the 1944-45 season Bill managed to stay out of the penalty box for the entire season which assured him of the Lady Byng Trophy that year.

In 1944-46, Johnny Gottselig, coach of the Chicago Black Hawks put Mosienko together with the Bentley Brothers, Max and Doug and the trio formed the famed "Pony Line". In the 1946-47 season the Pony Line scored 179 points to lead the league as the top scoring line. On March 23, 1952 Bill scored his famed 3 goals in just 21 seconds. At that same time another record, perhaps lesser known was also established, and that was the fastest 3 assists by one player. Gus Bodnar was Mosienko's line mate at the time and he assisted on all 3 of Bill's goals. Jean Beliveau holds the second place position for the fastest 3 goals at 44 seconds, and coincidently his line mate, Bert Olmstead also assisted Beliveau on all three goals.

Bill retired from the NHL at the end of the 1955 season. During his career he was selected to the NHL Second All Star Team in 1945 and 1946, and won the Lady Byng Trophy in 1945. He was also selected to the WHL Prairie Division First All Star Team in 1957, 1958 and 1959. Bill played in the NHL All Star game in 1947, 1949, 1950, 1952 and 1953. After retiring from the NHL, Bill helped to establish the Winnipeg Warriors of the WHL where he played for 4 years before coaching them in the 1959-60 season. Bill was elected to the Hockey Hall of Fame in 1965.