2010-11: Darnell Nurse appeared in two OJHL games with the St. Michael's Buzzers and skated for the Don Mills Flyers midget minor AAA team in the Greater Toronto Metro league. He was scoreless with 4 penalty minutes for the Buzzers. In 38 games with Don Mills he scored 11 goals with 18 assists and had 72 penalty minutes. The Flyers participated in the OHL Cup and in seven games Nurse scored 2 goals with 3 assists and had 18 penalty minutes. Nurse was selected by the Sault Ste. Marie Greyhounds in the first round (third overall) of the 2011 OHL Priority Selection.
2011-12: Nurse played in 53 games for Sault Ste. Marie in his first OHL season, represented Canada Ontario in the 2011 U17 World Hockey Challenge and played for Team Canada in the 2012 U18 World Junior Championship. He scored 1 goal with 9 assists and had 61 penalty minutes; finishing minus-15 as the Greyhounds missed the OHL playoffs. Nurse scored 1 goal with 2 assists in five games for Canada Ontario at the WHC and skated in seven games for Canada's bronze medal-winning U18 team; finishing plus-four with no points and 4 penalty minutes.
2012-13: Nurse was a big part of the Greyhounds success as Sault Ste. Marie reached the OHL playoffs for the first time in three seasons. An assistant captain, he was the only player to skate in all 68 regular season games and scored 12 goals with 29 assists; finishing plus-15 with a team-high 116 penalty minutes. In the six-game playoff series with Owen Sound he scored 1 goal with 3 assists and was minus-1 with 6 penalty minutes. Nurse was selected to play for Canada in the 2013 U18 World Junior Championships and was rated ninth amongst North American skaters in Central Scouting's mid-term rankings prior to the 2013 NHL Draft, and fourth in the CSS final rankings.