Joe McKnight was drafted by the New York Jets in the fourth round (112th overall) of the 2010 NFL Draft. To select McKnight, the Jets traded up twelve spots in the fourth round with the Carolina Panthers. In return, the Jets sent their fourth (124th overall) and sixth (198th overall) round selections to Carolina. McKnight formally signed with the Jets on June 22, 2010. Joe McKnight struggled in the early stages of his professional career, vomiting during the Jets’ rookie minicamp in May 2010. McKnight later admitted he had not been in proper condition at the time. He continued to struggle into the preseason, fumbling the football three times. Though he was not in danger of being released from the team, it was maintained that McKnight would not appear on the active roster until the coaches felt more confident in his abilities. McKnight made his NFL debut on October 3, 2010, against the Buffalo Bills and was used in a limited capacity on offense before being utilized as an emergency cornerback and on special teams over the course of the season. In McKnight’s first game as the starting running back, against the Bills during the Jets’ final regular season contest, McKnight ran for 158 yards on 32 carries with no fumbles and caught two passes for 15 yards. During the Jets’ 2011 home opener against the Dallas Cowboys on September 11, 2011, McKnight blocked Matt McBriar’s punt on a critical play resulting in a touchdown by fellow defender Isaiah Trufant. The Jets went on to defeat the Cowboys 27–24. During the Jets’ Sunday night game against the Baltimore Ravens, on October 2, 2011, Joe McKnight returned a kickoff for 107 yards, his first career touchdown. It was the longest play in Jets history. On January 16, 2012, McKnight was named as the Kick Returner for All-Pro team By Pro Football Weekly / Pro Football Writers Association.

On September 26, 2012, Jets head coach Rex Ryan announced that McKnight would see an increase in defensive snaps at cornerback. The announcement was prompted after Darrelle Revis suffered a season-ending ACL tear. Shortly after the announcement was made, Joe McKnight was switched back to his former role as a running back. On October 8, 2012, McKnight returned a 100-yard kickoff for a touchdown against the Houston Texans, recording his second career touchdown. Elias Sports Bureau reported that McKnight had extended the Jets’ NFL record of most consecutive years with a kickoff return for a touchdown to 11 years. He was released by the Jets on August 26, 2013. After spending the entire 2013 year out of football, McKnight signed with the Kansas City Chiefs on January 12, 2014. On July 21, McKnight was placed on the Physically Unable to Perform list. On September 21, 2014, in a game against the Miami Dolphins, he scored two times on receptions from Alex Smith. McKnight suffered a torn Achilles tendon during practice on September 26, 2014, and was ruled out for the rest of the 2014 season. On December 1, 2016, Joe McKnight was fatally shot by 54-year-old Ronald Gasser at an intersection in Terrytown, Louisiana, in what the media claim to be a road rage shooting. McKnight exited his vehicle and approached Gasser’s car when he was shot by Gasser who was still in his own vehicle. An initial media report claimed that after firing the initial shot, Gasser reportedly stood over McKnight and said “I told you not to fuck with me” after which, he fired another shot. However, this was disputed by Jefferson Parish Sheriff’s Office, which stated that forensic evidence suggested Gasser fired the shots in quick succession from within his car. McKnight was reportedly unarmed. Gasser remained at the scene and turned in his gun to police. The Jefferson Parish Sheriff’s Office took Gasser into custody for questioning, and released him without pressing charges while the investigation continued. Gasser was arrested on December 5, 2016, on the charge of manslaughter.