Newsome was selected in the fifth round (164th overall) of the 2014 NFL draft by the Indianapolis Colts, the first Ball State player to be drafted by the Colts. He recorded his first NFL tackle on the September 21, 2014 in the Colts win over the Jacksonville Jaguars. In week 9, playing against the New York Giants, he recorded 7 tackles, 2 sacks, and 1 forced fumble. Newsome made his first career start in week 17, and went on to win the AFC Defensive Player of the Week award for his performance. He finished the game with 8 tackles, 1 forced fumble, and 2 sacks. Newsome finished the season with a team-leading 6.5 total sacks, the second-most amongst NFL rookies in 2014 and the third most by a rookie in Colts' franchise history. Jonathan was released from the Indianapolis Colts on February 22, 2016, after being arrested by police for marijuana possession.