Muskett first won the national title in 2002 and also won in 2009 and last year.
Muskett (58) was followed closely for the first 50km by Canterbury's Shannon Littl but pulled away over the last 50km and eventually lapped her.
Muskett won in 10hr 5min and was 9min ahead of Littl at the finish.
Marty Lukes (Canterbury) was not troubled in retaining his men's title in a world-class 7hr 8min on the 2km asphalt course.
He was followed home by New Zealand 24-hour representative Bryan McCorkindale (Canterbury) in 8hr 13min, with Caversham's Glenn Sutton third in 8hr 30min.
Muskett has competed in the 100km internationally five times and will continue her international career in September when she competes at the world 24-hour championships in Katowice, Poland.
Her best international performance was to finish 11th at the world 24-hour challenge in South Korea in 2008, when she covered 205.14km in Seoul.
Finalists for the Otago Athlete of the Year awards
Winter female: Rebekah Greene (Hill City-University), Shauna Pali (Hill City-University), Rozie Robinson (Hill City-University).
Winter male: Dougal Thorburn (Ariki), Callan Moody (Ariki), Daniel Balchin (Caversham).
Summer junior: Holly Robinson (Taieri), Rebekah Greene (Hill City-University), Andrew Whyte (Hill City-University).
Summer senior: Marshall Hall (Taieri), Winifred Harding (Taieri), Rozie Robinson (Hill City-University).
