In 1995, Grant moved up to the Major Series Lacrosse (MSL) with the Peterborough Lakers, where he won the Top Rookie of the Year award.

In 2002 and 2003, Grant moved west, playing in the Western Lacrosse Association with the Coquitlam Adanacs, earning All-Star recognition.

Grant came back to the Peterborough Lakers in 2004 and led the team to a Mann Cup victory, earning the Mike Kelley Memorial Trophy as the competition's Most Valuable Player.

[8] Grant suited up for the Peterborough Lakers of Major Series Lacrosse on July 9, 2009, a surprisingly early comeback from his surgery.

Grant was drafted by the Buffalo Bandits in 1995, but he didn't sign, instead opting to attend junior college at SUNY Morrisville playing for future Yale coach Andy Shay.

Grant transferred to the University of Delaware and played the 1998 and 1999 seasons, again teaming up with Shay who had moved there as an assistant, with the Fightin' Blue Hens compiling a 23 and 8 during that time.

John led the school to its first ever NCAA quarterfinal appearance as well as its first 14-win season, with victories over perennial lacrosse powers North Carolina, Navy and Towson, in addition to 4 other top 20 teams.

In 2007 Grant set a National Lacrosse League record with 15 points in a single game (9 goals, 6 assists) in a win over the New York Titans, since broken by Mark Steenhuis.

[13] Draft picks were also exchanged in the trade, which the Knighthawks said they executed to alleviate the effects of an aging roster, despite being reluctant to deal Grant after such a long and successful tenure in Rochester.

[21] Grant Jr. was traded to the Denver Outlaws,[22] along with defenseman Michael Simon, in exchange for attackman Brendan Mundorf and the 16th pick in the 2014 collegiate draft in September 2013.

Grant Jr. helped the Machine get to their first championship game that summer, but faced his former team in the Denver Outlaws, who had rattled off seven straight victories.

[26] He entered the season only needing five points to surpass Paul Rabil as the all-time leading scorer in MLL history.

He hit this mark on June 9 in an 18–16 win over the Atlanta Blaze[27] On July 9, the league announced the 44-year-old John Grant Jr. had been selected to the MLL All Star Game.

[28] On June 18, 2022, Grant was inducted into the Professional Lacrosse Hall of Fame as one of the eleven members of the inaugural class of inductees.