The Jamaica international will be in charge for the 2023/24 season.
The 35-year-old has previously managed Kendal Town and Penrith and played at Garstang.
A Milnthorpe spokesman said: "Following the resignation of Shaun Gardner last weekend the club are delighted to announce the appointment of former Preston North End player Chris Humphrey as their new 1st team manager with immediate effect.
"The club would like to thank all applicants for the post and wish them well for the future."
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