McCaffrey was selected by the Giants in the third round (83rd overall) in the 1991 NFL draft. During his thirteen-year career, he won three Super Bowl rings (Super Bowl XXIX, as a 49er; XXXII and XXXIII, as a Bronco) and made a Pro Bowl appearance in 1998. At Denver, he became a reliable target for quarterback John Elway, set a Broncos record for most receptions in a season (with 101 receptions in 2000), and had an exceptional performance in Super Bowl XXXIII, recording five catches for 72 yards. Also in 2000, McCaffrey and teammate Rod Smith became only the second wide receiver duo from the same team to each gain 100 receptions in the same season (see Herman Moore and Brett Perriman).
In the opening game of the Broncos' 2001 season, McCaffrey suffered a leg fracture while playing a Monday Night Football game with the Broncos against the Giants. He rebounded in the 2002 season with 69 receptions and 903 yards. Hampered by injuries during a disappointing 2003 season, McCaffrey retired on February 29, 2004. He finished his career with 565 career receptions for 7,422 yards and 55 touchdowns.
McCaffrey is the oldest of five children, with two brothers and two sisters: Monica (who played basketball at Georgetown University), Billy (who played basketball at Duke and Vanderbilt), Michael, and Meghan.
McCaffrey began coaching youth football camps in the summer of 2000. In 2011, he founded SportsEddy, which includes not just football but lacrosse, soccer, baseball and basketball camps. The Ed McCaffrey "Dare to Play" football camp and the "Dare to Cheer" cheerleading camp for individuals with Down syndrome are produced in partnership with the Global Down Syndrome Foundation. McCaffrey also founded the McCaffrey Family Foundation with wife Lisa, to assist children whose medical situation has created an academic or financial hardship.
He also has his own brand of mustard and horseradish sauce, which can be found in supermarkets across Colorado and into Nebraska. On July 30, 2012, McCaffrey was named the new color analyst for 850 KOA, flagship station of the Denver Broncos Radio Network, replacing Brian Griese.
On November 15, 2017 McCaffrey lit the brewery lights at the Fort Collins Brewery with brewmaster Tim Seitz.
Together, they have four sons, all of whom play football. The oldest son, Max McCaffrey, is a wide receiver who played college football at Duke. He was on the rosters of several different NFL teams from 2016–2018 and is currently a free agent.
The youngest son, Luke McCaffrey, is a 2018–2019 senior at Valor Christian High School, expected to graduate in May 2019. Luke has also received an offer from Michigan, along with an offer from Nebraska. He committed to Nebraska in June 2018.
|center|border|160x170px|alt=|Max, eldest son of McCaffrey
Max, eldest son of McCaffrey
[[File:Christian McCaffrey with fan, Jan 2019 (1).jpg
|center|border|160x170px|alt=|Christian, second-eldest son of McCaffrey
Christian, second-eldest son of McCaffrey
[[File:Dylan McCaffrey (45337580).jpg
|center|border|160x170px|alt=|Dylan, third-eldest son of McCaffrey