Former Australia One-day batsman Di Venuto, 30, is set to be sidelined for at least four months after undergoing back surgery having sustained an injury while playing for his native Tasmania.
Di Venuto, who was due to succeed ex-England all-rounder Dominic Cork as Derbyshire skipper, is the second Tasmanian to be forced out from appearing for the midlands side before the English season has even started. All-rounder Damien Wright was also sidelined because of a knee injury.
"We don't think Mike will take on any part for us this season but he remains a big part of our future," former Zimbabwe captain and coach Houghton said.
"We have known about his problem for a while now and have got a contingency plan in place," added Houghton as he prepared for his first season in charge of Derbyshire.
"That has not been fully finalised as yet because we wanted to give Mike that final one per cent chance that he might get away with not having an operation ". Wicketkeeper Luke Sutton replaces Di Venuto as captain.
Meanwhile the club as a whole will be looking to get off the bottom of the table after finishing last in the 2003 County Championship, English cricket's domestic first-class competition.
Despite Derbyshire's poor performance last season Di Venuto still managed to score 1,520 first-class runs including five hundreds.
But Houghton said: "Lifting us from the bottom is not about one person, it is about building a club and we are hopeful we have an adequate replacement."
Derbyshire are due to name their second overseas player within the next few days having already signed Victoria all-rounder Jonathon Moss, who scored 98 and took three for 18 in the final of the Sheffield Shield against Queensland earlier this month, in place of Wright.