Frank first played professional for the Port Arthur Bearcats of the Northern Ontario Hockey League in 1911. Fellow Pembroke native Harry Cameron was invited to play for Port Arthur but refused to go without Nighbor. The club agreed to bring Nighbor along, but they left him on the bench until injuries gave him an opportunity to play. He made the most of his opportunity by registering six goals in his first appearance.
In 1912, he joined the new Toronto Blueshirts of the NHA where he scored 25 goals in 18 games. He only played the one season in Toronto, jumping to Vancouver of the PCHA the following season for two seasons, and was an important member of the Millionaires team which won the Stanley Cup over the Ottawa Senators in 1915.
He returned east after the Stanley Cup series and joined the Senators, whom he would play for until 1930, an important part of the dynasty of the 1920s winning 4 more cups in 1920-21-23-27. He had his best season in 1916-17, scoring 41 goals in 19 games, finishing tied for the league lead with Joe Malone. In 1919-20 he would score 26 goals and 15 assists in just 23 games, then had a further 6 goals in 5 playoff games and led the Senators to their first Cup in the NHL. Frank would win the Stanley Cup again with Ottawa in 1921 1923 and 1927. As a member of the Senators, Frank was the first recipient of the Hart Trophy, as well as the first recipient of the Lady Byng Trophy.
Frank coached for the Buffalo Bisons and London Tecumsehs of the International League and the New York Rovers of the East Coast Hockey League. He would later turn to an insurance business he was a partner in and run it until he became ill. He was inducted into the Hockey Hall of Fame in 1947. He has also been inducted into the Canada Sports Hall of Fame and the Ottawa Sports Hall of Fame. In 1998 he was ranked number 100 on The Hockey News' list of the 100 Greatest Hockey Players.
|1914-15||Vancouver Millionaires||Stanley Cup||3||4||6||10||6||-||-||-||-||-|
|1929-30||Toronto Maple Leafs||NHL||22||2||0||2||0||-||-||-||-||-|