The 34-year-old signed for Phillip Cocu's men in January and has scored four times in 12 appearances for the Rams, with bet365 going 21/10 (3.10) that he adds to that tally against his former club on Thursday.
Rooney scored 253 goals in 559 games for the Red Devils and is their highest-scorer of all-time, but failed to strike in either of his two matches against them after leaving the club.
However, with a goal in three of his last four games at Pride Park, the former United forward will look to keep that run going against the club where he spent 13 years.
Two of the four goals he has scored this season have been the first of their respective matches and he can be backed at 7/1 (8.0) to repeat the feat here.
With Derby floundering in mid-table in the Championship, Cocu will certainly look to continue their FA Cup campaign and they are likely to attract some attention at 5/1 (6.0) to win.
The Rams have not got past the fifth round of the cup since 1999 - when, coincidentally, United lifted the trophy - and are 11/4 (3.75) to qualify for the quarter-finals by any means including extra time and penalties.
Derby's 3-1 win at Sheffield Wednesday on Saturday arrested a four-match winless run and so will give them confidence for this one, but Ole Gunnar Solskjaer's side, though, are in a rich vein of form.
Indeed, the visitors are unbeaten in their last eight fixtures in all competitions, which is their longest run since they went 11 without defeat from December 2018 to February 2019.
Backing the Red Devils to qualify pays out at 1/4 (1.25) and although United are still chasing Champions League football, Solskjaer will surely also be targeting his first piece of silverware in charge of the club.
Odds correct at the time of writing. Please gamble responsibly.