Luck, 26, had been limited in practice this week by an injury to his throwing shoulder, and was listed as questionable for Sunday's game on the Colts' Thursday injury report.
Colts backup quarterbacks Matt Hasselbeck and Alex Tanney filled in for Luck in practice leading up to the Week 4 matchup, and the team also signed quarterback Josh Johnson on Friday to have as another signal-calling option.
This season, the former No. 1 overall pick out of Stanford has five touchdowns, seven interceptions and one fumble through three games. His 65.0 passer rating is currently the league's worst.
In four years in Indianapolis, Luck had never missed a start.
The Colts (1–2) host the Jaguars (1–2) at Lucas Oil Stadium at 1 p.m. ET on Sunday.
- Kayla Lombardo