Byrne arrived in Cambridge from Notre Dame where he was an assistant coach for 16 seasons, covering two stints. His first stop in South Bend, Indiana, was from 1989-91, before returning in 2007. In between, Byrne served as head coach at Saint Anselm College in Manchester, New Hampshire, from 2003-06.

Byrne helped the Fighting Irish to 14 NCAA tournament appearances (including 13 straight), 11 conference titles (regular season and tournament), and an overall record of 170-78 (.685). More impressive was the impact Notre Dame, which earned one of eight national seeds in 11 of the last 12 years, had once in the NCAA field as it reached the quarterfinal round or later on 10 different occasions, twice earning a spot in the finals (2010, 2014).

Over his final 13 seasons at Notre Dame, Byrne helped tutor 62 United States Intercollegiate Lacrosse Association (USILA) All-Americans, with 15 of those selections earning first-team honors, and 13 USILA Scholar All-Americans. During Byrne's tenure, UND was also awarded the USILA Kelly Award (most outstanding goalie in NCAA Division I) twice and the USILA Schmeisser Award (top defensive player) three times.

Byrne's work did not go unnoticed as he was named the 2011 Intercollegiate Men's Lacrosse Coaches Association National Assistant Coach of the Year and was on the top coaching staff at the conference level three times, winning the coaching-staff-of-the-year award in the Great Western Lacrosse League twice (2007, 2009) and once in the Big EAST (2012).

Under Byrne's watch, Notre Dame was one of the top defensive teams in the country. The Fighting Irish finished among the top five nationally in scoring defense seven times in the last 13 seasons, producing the nation's stingiest group in 2009 and 2012. The 2012 club also boasted the best man-down defense in Division I. In his final season in South Bend, Notre Dame finished the 2019 campaign ranked 14th in scoring defense and ninth in clearing percentage.

Additionally, Byrne helped the Fighting Irish hold its opponents to seven goals or fewer in 50.2 percent of their games (103-of-205) since the start of the 2007 campaign and limited its foes to four goals or less on 19 occasions.

While at Saint Anselm College, Byrne guided the Hawks to 16 victories with the 2005 squad setting the program record for lowest GAA, face-off winning percentage and ground balls in a season.