Fournette is nursing a troublesome hamstring injury for the Jaguars (3-2), who are once again expected to lean on fellow running back T.J. Yeldon. Jamaal Charles was signed as a free agent on Tuesday to help a backfield that also saw Corey Grant placed on injured reserve with a foot injury.
Yeldon has rushed for 258 yards and reeled in 22 passes for 194 yards while taking on the lead role for the Jaguars in Fournette's absence.
Head coach Doug Marrone also ruled out left tackle Josh Wells (groin) for Sunday's game versus the Cowboys. Josh Walker likely will get the start in place of Wells, who took over after Cam Robinson's season-ending ACL injury.
Cornerback D.J. Hayden will miss his fourth straight game with a toe injury.
Fournette aggravated his right hamstring during a 31-12 win over the New York Jets on Sept. 30. The 23-year-old sustained the original injury in the first half of the season opener against the New York Giants.
The 6-foot-1, 223-pound Fournette has rushed for 71 yards on 20 carries this season.
Fournette led the Jaguars in rushing during his rookie season with 1,040 yards on 268 attempts and nine touchdowns in 13 games a year ago.
Jacksonville's first-round pick (No. 4 overall) in the 2017 NFL Draft, Fournette missed three games last year -- two due to an ankle injury and one game with a quadriceps injury.