Cubs manager Mike Quade had Castro and Darwin Barney batting 1-2 to open the series against the Cardinals.
"We'll start with those two kids, and it will be an evolving thing -- and maybe not," Quade said.
It's not a new role for Castro, who has a .369 average in 19 games as the leadoff man.
Fukudome had the best on-base percentage on the team, and Castro and Barney aren't the most patient hitters.
"They may not walk as much, but I still see Barney work counts, and there's going to be a day when he's 3-2 and 2-2 [in the count] and takes a couple pitches and walks," Quade said of the second baseman. "He does work the count and he also allows me to play some hit-and-run and do things at the top of the order. [Leading off] will give 'Cassie' some freedom to run."